Dr. Ewen Keenan met Elizabeth Webber when he posed as a patient at Shadybrook during her brief stay at the psychiatric care facility. The two bonded over a discussion on painting until Ewen handed her his card and Elizabeth realized he was a doctor, not a fellow patient. Elizabeth forgave Ewen's deception when he visited her at her home and gave her paints so she could resume painting, the hobby she used to love. Ewen and Elizabeth crossed paths often at General Hospital and she enjoyed his unconventional approach to therapy.

Ewen spent a great deal of time at Wyndemere treating a patient with amnesia that he named Cassandra. Both Damian Spinelli and Ethan Lovett had expressed a romantic interest in his patient, although Ewen recommended that Cassandra not enter into any sort of relationship. He admitted that Cassandra had shown up in his office months earlier and written a note asking him to help her reclaim her life. Ewen was puzzled by her memory loss as he was unable to discover a physical reason behind it. He was not even sure of Cassandra's real name.

Cassandra insisted on staying at Wyndemere so Ewen made arrangements to stay there with her. She was unable to explain her connection to the place or her fascination with a portrait of Laura Spencer. While Ewen continued to work at the hospital and with Cassandra, he also consulted with the police and created a profile about the person that was attacking exotic dancers in the city.

Ewen also offered his psychiatric services to Kate Howard after he encountered her on the pier wearing a wedding dress covered in blood. She admitted she suffered black-outs and found clothing and notes and numbers that she did not recall. Kate took off when Ewen offered to help her but she called him a couple of weeks later. She continued to experience chunks of time she could not account for and Ewen suggested that she might have Dissociative Identity Disorder (DID).

Kate eventually decided that she needed Ewen's help and he brought out her alter using hypnosis during a therapy session. The other personality introduced herself as Connie and explained that she was trying to save Kate's life by orchestrating the end of Kate's relationship with Sonny although she would not divulge how she intended to do so. When Kate regained control, she and Ewen both wondered if Connie had something to do with a gun that was found in Kate's office. The gun was considered a piece of evidence against Sonny Corinthos in a police investigation.

As Ewen continued to work with Kate, he found time to develop a friendship with Elizabeth. He confessed that he had been the one to save her from drowning a few months earlier after she had been knocked unconscious and thrown overboard by Lisa Niles. Elizabeth wondered why Ewen had not originally revealed that he had saved her and he explained that at the time he had been preoccupied with Cassandra and had not wanted to draw any attention to her. As the time passed he felt awkward bringing up the rescue so he had not said anything.

After the secret about the rescue was out in the open, Ewen asked Elizabeth on a date. She accepted and he shared his ability to play the harmonica with her and they talked a bit about Jasper Jax and his brother Jerry. She revealed that she had been held hostage by Jerry when he had taken over the Metro Court Hotel. Ewen's comments hinted that he knew the Jacks family although he claimed he did not. Their date was cut short when Kate's alternate personality Connie interrupted them and demanded Ewen's attention.

Ewen made plans to commit Kate for psychiatric care after he determined that her alternate personality could cause harm to Kate or to someone else. As he worked on the paperwork, he met Steven Webber's mother, Heather. She had recently been released from Ferncliff psychiatric care facility and Ewen decided she also needed to see him for therapy sessions.

Kate reached out to Ewen after Connie successfully carried out her plan for revenge by sleeping with Sonny's rival Johnny Zacchara. Kate was distraught by Connie's actions and agreed that she needed to be admitted immediately to Shadybrook. When Ewen and Kate stopped by Ewen's office to retrieve the paperwork he had prepared, Connie emerged again and clobbered Ewen over the head with a paperweight. He was rendered unconscious while Connie escaped.

Elizabeth discovered Ewen on the floor of his office and she checked on him often after he was admitted to the hospital as a patient. The injury Ewen had sustained required him to undergo brain surgery which was performed by Patrick Drake. Once Ewen awoke after surgery, he asked to see Elizabeth and they shared a kiss. After Ewen was released, he and Elizabeth decided to try another date but Ewen wondered if Elizabeth had feelings for Jason Morgan after he saw them together.

Meanwhile, Ewen resumed his work with Kate and helped her uncover the trauma that had initiated her dissociative identity disorder. Ewen also started counseling Patrick for his addiction to amphetamines. Patrick admitted that he had turned to the pills to deal with the grief he felt after his wife Robin had died unexpectedly.

As Ewen continued his work at General Hospital, he gave a nurse at Ferncliff orders to carry out electroshock treatments on a patient. When the patient did not respond as he had hoped he visited the patient who was Patrick's presumed-deceased wife Robin. He told Robin that she would be moving to a clinic in Switzerland since her mother was close to discovering that she was still alive. Afterwards, Ewen spoke to someone on the phone and informed the person that Robin needed to be moved. That person was Jerry Jacks.

Jerry summoned Ewen to meet with him at Wyndemere and warned him not to reveal any secrets to Elizabeth Webber. Ewen was disturbed when he realized that Jerry had been watching so closely and warned him to stay away from Elizabeth. Ewen met with Elizabeth and planned to come clean about his association with Jerry and the involvement in faking Robin's death. As the conversation started, Jerry sent Ewen a text ordering him to stop the conversation. Ewen heeded the warning and instead confessed to Elizabeth that he cared deeply for her.

The feelings Ewen had for Elizabeth became Jerry's leverage over him when he protested his next task. Jerry instructed Ewen to kidnap Josslyn Jacks but Ewen protested the abduction of a young child. Jerry told Ewen that if he did not comply, Elizabeth would learn about what Ewen had done to Robin and her family. In the end, Ewen did as he was told and brought Josslyn to Jerry. When he arrived at Wyndemere with the child he found Alexis Davis unconscious on a couch and he questioned Jerry about what he had done to her. Jerry refused to confide in Ewen but allowed him to return Josslyn to her home after she was injected with a syringe that contained a mysterious substance. Alexis had also been injected with the same substance.

Ewen was overcome with guilt regarding his knowledge of Jerry's actions and he returned to Wyndemere to press him for more information about what he had done to Josslyn and Alexis since both had been hospitalized. When he arrived at Wyndemere Jerry was gone but Jason Morgan and John McBain were there looking for clues as they theorized that whomever had injected Josslyn and Alexis had done so at Wyndemere. Both John and Jason were suspicious of Ewen's presence there and he claimed that he had been contacted by the security company that watched over the house since some of his belongings remained in storage there. The men wondered if Ewen had been behind the injections and they questioned him. Ewen was not convinced that Jason and John believed his story but he resumed his work at the hospital and worried about the health of Alexis and Josslyn. He was relieved when they both made a full recovery.

Ewen moved forward in his relationship with Elizabeth and made it clear to her that he was ready to spend the night with her. She admitted that she cared for him but wanted to take things slow. Ewen spent the spent the night on her couch after he had a little too much to drink. The next morning Ewen was rattled when Jason showed up to visit Elizabeth and he assumed that Jason was there to warn Elizabeth to stay away from him. Instead Jason apologized for suspecting him of harming Alexis and Josslyn. He accepted the apology and was paged to the hospital.

The patient that required Ewen's immediate care was Olivia Falconeri. She had been injected with LSD and continued to experience hallucinations. Ewen was rattled by Olivia's reaction to him after he entered her room and she hallucinated that he was the devil. Afterwards Ewen returned to Elizabeth's home and they watched Jerry broadcast on television that he had poisoned the water supply in Port Charles with a deadly toxin. As Jerry spoke Ewen unraveled and admitted that he had been working with Jerry. Elizabeth questioned Ewen's association with Jerry but he tried to cover his slip.

Both Ewen and Elizabeth had been exposed to the toxin but Elizabeth focused on the recognition that Ewen seemed to have of Jerry. As Ewen tried to reassure Elizabeth that he was innocent Patrick arrived. Ewen pretended to leave but actually sneaked up on Patrick and hit him over the head with a baseball bat and knocked him out. He then kidnapped Elizabeth and drove away with her. Elizabeth questioned Ewen about why he had taken her. He replied that he cared about her and wanted to protect her.

Eventually Ewen brought Elizabeth to their destination which turned out to be Ewen's residence in the country outside of town. He explained that the old building reminded him of the sheep farm he had grown up on in Australia before the Jacks family and taken it all away. Each of them started to show signs of sickness due to the toxin and Elizabeth encouraged Ewen to confess what he had done so he might be able to die with a clear conscience. Ewen told Elizabeth that his father had possessed the Dead Man's Hand set of cards until they were stolen away by Jerry's father John Jacks. The loss of the cards led to financial ruin for Ewen's family and his own father was distraught over the hardships that had befallen them and eventually died. Meanwhile, the Jacks family flourished once they had the cards. Ewen promised to make the Jacks family pay for what they had done to his father.

After the death of his father Ewen kept a close watch over the Jacks family and saw his opportunity for revenge. The cards were stolen away from John and he sunk into a deep depression. Ewen positioned himself as John's doctor and injected him with a powerful sedative. Immediately after Ewen delivered the injection, Jerry walked in and realized what Ewen had done. Jerry agreed to keep the secret that Ewen had killed John but held it over Ewen and used it to force Ewen to be his accomplice.

Elizabeth was shocked by Ewen's confession and gravely concerned when Ewen produced a gun. He reassured Elizabeth that he would never hurt her and clarified that he was going to use the gun to threaten Jerry into providing Elizabeth with the antidote to the toxin so her life would be saved. Ewen's plan was foiled when Jason arrived but he insisted that he, not Jason, would be the one to save Elizabeth. Both Jason and Elizabeth tried to reason with Ewen but used Elizabeth as a human shield against Jason and fired a shot into Jason's leg. Jason fired a return shot of his own into Ewen's chest.

The gunshot critically injured Ewen and he was taken to the hospital. Once there, Elizabeth's brother Steve attended to him but Ewen realized he was dying and lamented that he was not worth saving. He urged Steve to focus on other patients and Steve offered to send in a priest but Ewen requested Patrick instead. When Patrick arrived he questioned why Ewen wanted to see him. Ewen said it pertained to Robin but he succumbed to his injuries and passed away before he could elaborate.