House describes Wilson as "a buddy of mine people say 'Thank you' to, when he tells them they are dying."After Wilson suffers his third failed marriage, House theorizes that Wilson feels a need to "fix" the vulnerable women he meets, and when they become well-adjusted with Wilson's help, he becomes discontent and moves on.House also describes Wilson as an "emotional vampire".On a tarehe with Lisa Cuddy, Wilson evades a swali as to whether au not he wants children.

However, Wilson defends House when House's career is in jeopardy, after billionaire entrepreneur and then chairman of the hospital board Edward Vogler (Chi McBride) proposes a motion for House's dismissal.Wilson is the only one to vote against the motion. In response, Vogler proposes and succeeds in obtaining Wilson's dismissal from the board, but Wilson is soon reinstated thanks to Lisa Cuddy (Lisa Edelstein) after she convinces the board that Vogler is the real threat to the hospital and his money is not worth the business-obsessed mindset with which he tries to rule the hospital.In a late season three episode it is revealed that Wilson suffers from clinical depression and uses a prescription for his illness.Wilson is also seen to be left-handed, a trait he shares with Cuddy and Foreman.

Wilson attempts to change House's drug habits, with little success. After starting a bet to prove House's addiction to Vicodin, House concedes that he has an addiction, but says that the addiction is not a problem because it does not interfere with his work.It is, in fact, Wilson who usually writes House's Vicodin prescriptions (with Dr. Cuddy uandishi a few merely for leverage in her dealings with House). In Season 3, when Detective Michael Tritter (David Morse) threatens to jail House for his Vicodin addiction after finding a huge stash in his apartment, Wilson attempts to convince House to attend rehab as the situation worsens.After Tritter pressures Wilson to testify several times, Wilson reluctantly agrees, unknown to House. Before this, Wilson watches House ngumi, punch Dr. Robert Chase in a reaction to his detoxing, verbally insulting Cuddy and incorrectly diagnosing a child with a condition that would have required an amputation of one of her arms and legs.

Near the end of season 4, Wilson starts a romantic relationship with Amber Volakis,who competed for one of the open jobs on House's team in the wake of Foreman, Chase, and Cameron's departure. In the season finale, she dies as a result of a bus crash sustained while picking up a drunken House from a bar.Her death eventually leads Wilson to conclude that his relationship with House only serves to enable House's dysfunctions. To remove himself from House's influence, he resigns from Princeton-Plainsboro at the beginning of season 5, telling House that they are no longer friends, and that he wasn't sure they ever had been. The two reconcile when Wilson forces House to attend the funeral of House's father. Wilson realizes that he had been afraid of losing House. He then returns to Princeton Plainsboro.

During Season 5 it is revealed that Danny, one of Wilson's brothers (who had previously been mentioned as being homeless), suffered from schizophrenia since adolescence, which is what caused him to run away in the first place. Wilson blames himself for his brother's homelessness, having hung up on his brother right before he disappeared. Wilson also reveals to House that he took the position at Princeton-Plainsboro because it was near the place he had last seen Danny. When Wilson finds out that Danny is in the psych ward of New York Mercy, House offers to come with him to keep him company, noting that it could end badly. However, when Wilson is let in to see his brother, House is busy with a differential with his team.

Gay references have been made to the relationship between the two characters of the onyesha and House has made a joke about the relationship between them ("I'm gay!...Oh that's not what wewe meant. It would explain a lot, though: no girlfriend, always with Wilson, the obsession with sneakers..."). Barbara Barnett alisema that "House is the needy one in the relationship, and Wilson the doormat"Verne Gay of Newsday described House's upendo for Wilson as "touching and genuine". However, Robert Sean Leonard compared the relationship between the two characters to the relationship between Cesar Millan and his pitbull, while Hugh Laurie alisema that the relationship between the characters is "not just buddydom". The two characters appeared on the cover of the October 13, 2008 issue of TV Guide.In an interview with E!, executive producer Katie Jacobs stated that there are equal chances of either Cameron, Cuddy au Wilson "ending up"
with House.