Mental Illness
The underlying theme throughout this novel is that of mental illness. Although it is presented in a humorous way, the seriousness of the subject is dealt with by detailing the myriad of ways in which suffering from a mental illness can prevent a person from participating in life in the same way as everyone else. Don, the narrator, tells the reader in an almost throwaway manner that he was diagnosed as a teen with schizophrenia and that he still suffers from depression; as an extremely intellectually blessed man, he is able to recognize his own symptoms and ask for help with them or divert them himself, preventing his deepest depressions from becoming suicidal tendencies. Nonetheless, his borderline Asperger's prevents him from participating in the normal life stages a man of his education and means normally would. Asperger's is a "sub-theme" within the umbrella theme of mental illness as this is what afflicts Don's life in the present. We are shown the many ways in which this manifests itself, including obsessive-compulsive disorder and difficulty displaying empathy and establishing emotional connections. However, the novel also portrays Don as someone who is deserving of love and happiness without having to change or become someone different. The relationship between Don and Rosie is meaningful because Rosie loves Don unconditionally and honestly.
Reason versus Emotions
Because of his scientific training, personality, and implied potentially neuro-atypical identity, Don sees the world through a highly rational perspective. He often mistrusts or fails to understand why others make decisions from a place of emotion. When Don first devises The Wife Project, a series of questions that should produce the perfect partner for him, he attempts to apply a highly rational and analytical approach to the emotional process of falling in love. Part of Don's character development through the novel is him coming to realize that emotions sometimes defy logic: although it is implausible and irrational, he realizes that he loves being with Rosie and that she makes him happy.
Infidelity
Don's best friend Gene is what would have been described in Victorian times as a cad. His infidelity is one of the themes of the novel as his womanizing ways cast a shadow on both his marriage and the future of Don's relationship with Rosie, since Gene is the one advising Don on romantic matters most of the time. Especially because Don is naïve, inexperienced, and trusting, it is possible that Don will model his own behavior in romantic relationships based on the way he sees Gene behaving. However, over the course of the plot, it becomes clear that Gene's behavior is hurtful to Claudia and gradually eroding their marriage. Don, even while he is generally not emotionally astute, finally "calls out" Gene for his bad behavior. Infidelity is also an important theme because the whole Father Project is only necessary because Rosie's mother was unfaithful to her partner and therefore mistakenly believed that Phil was not Rosie's biological father. The reoccurrence of characters pursuing sexual relationships through infidelity shows that even intelligent people such as professors and doctors can still make impulsive choices that have potentially damaging consequences for people around them.
Parenthood
The Rosie Project is a search to identify Rosie's birth father. The theme of parenthood pits being a father against being a dad; Rosie believes that being a dad involves doing many things that her own "stepfather" has not done—she still remembers how upset she was at the cancellation of a Disney trip when she was eight. Because Rosie feels disappointed by Phil, she desires to find a different parent. The theme of parenthood shows that parents are human and cannot be perfect; unlike Rosie's notion of paternity, being a father does not mean that the person is entirely perfect, no more than being a dad does. The qualities needed for being a dad are ones that Phil has in spades, and Rosie's preoccupation with the identity of a biological father blinds her to the kindness, nurturing, and "dad" behavior with which she is already blessed.
Routine versus Spontaneity
At the start of the novel, Don maintains an incredibly rigid and structured routine. He feels that this routine helps him to be productive and efficient, but it also severely limits his ability to be adventurous and try new things. Don's relationship with Rosie also immediately impacts his routines because Rosie is quite spontaneous and adventurous. At first, Don cannot fully understand why he is tolerant of all the ways in which Rosie disrupts his routines, but this surprising behavior is an important clue that he might be falling in love with her. In time, Don himself takes the initiative to engage in adventurous and even risky behavior in order to help Rosie with her pursuit of finding her father. Because he cares about Rosie, he is willing to take risks in order to help her and have a reason to spend more time with her. Don's relationship with Rosie opens him up to new experiences, which is symbolized by how they move to a new city and a new country after they marry, and Don starts to try out a new line of work by working part-time in a cocktail bar.
Appearances versus Reality
Throughout the novel, various characters have to confront the idea that their initial assumptions may not have been correct. At first, Don is quick to assume that Rosie is not intelligent because he knows that she works at a bar, and he fixates on this detail about her. However, Don subsequently learns that Rosie is highly intelligent and pursuing her Ph.D. Likewise, Rosie at first thinks Don is very strange and uptight, but she is gradually won over by his earnest desire to help her. The idea of two people forming mistaken impressions of one another and then gradually having those ideas corrected has long been a theme of romantic comedies; Austen's Pride and Prejudice is a significant example. In the end, Rosie and Don both grow and change because of their relationship with one another, but they also accept each other and alter their initial impressions to be more balanced and realistic.
Social Acceptance
Social acceptance is a prominent theme in a novel where the protagonist is often blissfully unaware of all the ways in which he is different from others. This theme begins with the children who have Asperger's, as Don manages to encourage them to acknowledge their Asperger's and even feel pride in it, which is something that social convention has required them to do. Don does not fit with the general social conventions either, but this rarely bothers him. Many of the things needed to achieve this are shown to be rather inconsequential; Don makes some mistakes in social convention that might make others embarrassed or uncomfortable, but he is seldom bothered. While Don can be awkward, he is also highly intelligent, high-achieving, and capable of being a caring friend and partner. Don only abandons his identity to pursue a more socially conforming identity when he mistakenly believes that he needs to adopt a persona in order to win Rosie's love. Significantly, Rosie only accepts Don's marriage proposal once he accepts himself for who he is.