James Wilson

Wilson is by all standards one of the nicest people you could meet, as he has an unbelievable bedside manner and knows exactly how to talk to people. He also cares deeply about others, sometimes even more than he cares about himself. Patients have been known to thank him after he tells them that they're dying. He has donated blood and even organs to his patients when they cannot find matches. In the Season 6 episode, Lockdown, Dr. Remy "Thirteen" Hadley teases him, saying that he's too much of a "nice boy". He is "incapable of turning away from any responsibility" and ultimately believes that "enduring pain for someone you care about" is what life is all about. However, despite this, Wilson doesn't seem to acknowledge or realize that House admitted to being abused by his father as shown at his father's funeral.

In contrast to his own personality and demeanor, Wilson generally finds friends in much darker and more dour people, such as his best friend House or girlfriend Amber. In fact, House and Wilson are so very different from each other, that the close pair of friends can be said to be "polar opposites." This social life issue causes Wilson a great deal of frustration at times. This trait makes Wilson the only person who is willing to be with House on such a close and personal level of friendship.

In addition, as House often criticizes him for, Wilson tends to be a "clingy" friend/date. This is because of how much he cares about other people, resulting in him wanting to be as involved with them as possible.

He has also demonstrated that he caves in to people's demands too easily and has trouble forming his own opinions. In the Season 3 episode, Family, House lashes out at Wilson for leaving a major decision up to the parents of a patient, and when asked what he would recommend, he simply tells the parents that it's their decision. Also, in the Season 4 episode, Living The Dream, his girlfriend, Amber Volakis, tells him that the reason that his previous marriages didn't work out was because he did whatever they wanted and he ended up resenting them. She also angrily tells him "don't you ever do that to me". This is also shown by his inability to pick his own furniture in the Season 6 episode, Black Hole, displaying how he had always placed other's needs over his own to the point he didn't even know what he himself wanted, and when asked to pick one piece of furniture to define him, he finally picks out an organ for House instead, choosing to define himself by his relationship with others (particularly House). In Season 8, Wilson even agrees to undergo debilitating chemotherapy in order to extend his lifetime for House's sake, despite not wanting the treatment for himself. Wilson constantly enables House, including drug abuse and rude behavior, but on occasion stands up to him, usually for his own good, such as refusing to help him escape the psych ward in "Broken," or refusing to take the fall for a vandalism charge in Season 8.

While Wilson is normally a calm, serious person, he does have a humorous and playful side, as well. This especially happens when he is in a good emotional state, and/or when people play pranks with him. He has also proven many times that he is more than capable of getting his own back and even outwitting House with such examples being during the Season 2 episode, Safe where Wilson successfully sawed through House's cane so that it broke when House put his full weight on it, in the Season 3 episode, Resignation where he dosed House with antidepressants, in the Season 5 episode, Not Cancer, having learnt that House had a private eye to spy on him, Wilson deliberately hired a prostitute for a short visit and planted drug paraphernalia in his own garbage and then in the Season 8 episode, Perils of Paranoia where Wilson successfully locked House in the bathroom, giving House an evil smile which had House remarking, "Touché".

Despite his kind, and sometimes humorous nature, Wilson does occasionally get in a cranky mood. This typically happens when House pushes him to his limits, or when his issues just become difficult to handle, in general. There have also been times where Wilson has expressed some outrage or anger towards Cuddy, House himself and even some of House's team, usually for some emotional failure. This usually manifests in him "going off" on them, but is usually brief, and he typically makes up with them quickly. This happens a number of times with House. He also suffers from depression, for which he has been clinically treated. According to actor Robert Sean Leonard, he describes Wilson as "the saddest man alive... he's very lonely and a very spooky character", showing that he does suffer from a dark side.

Wilson also occasionally gets petty, such as with germs and keeping food safe, and with keeping his furniture clean.