Ryan forms a unique connection with his neighbor's dog after a failed suicide attempt.
Wilfred comes into Ryan's yard, so the two go to the beach, as Wilfred has always wanted to swim in the ocean. After Ryan lets him, the two bond more, and spend the day hanging out. When Ryan drops Wilfred off, Jenna asks Ryan to trick Wilfred into going to the dentist to get his teeth cleaned. Ryan reluctantly accepts, and tricks Wilfred by telling him they're going to the movies, and Wilfred is mad at Ryan. While under anesthesia, Wilfred reveals a horrifying secret about Jenna.
Ryan gets his wallet back (that's the good news) when his malevolent, porn-addicted neighbor Spencer (Ethan Suplee) shows up. The bad news: Spencer's looking for answers about who broke into his house. He's also looking for blood.
Ryan tries to reconcile with his sister (Dorian Brown), and Wilfred is in for a shock at doggy day care as a result.
Wilfred reveals an extraordinary ability when Ryan takes him to a hospice to volunteer.
Wilfred persuades Ryan to help him get rid of Jenna’s boyfriend.
Ryan must swallow his pride when Wilfred pursues a new love interest., and Ryan meets a new romantic interest (Jane Kaczmarek) himself
Ryan has a guilt complex over the death of his childhood dog, and Wilfred, upon learning of it, goes to otherworldly lengths to help Ryan discover the truth about how the pooch passed on. Meanwhile, Kristen throws a party for her boss (Nestor Carbonell).
Ryan's resentment of his mother even grows when she moves in and becomes friends with Wilfred.
Wilfred tries to find Ryan a human friend.
Ryan meets someone who questions Ryan's friendship to Wilfred.
Just as Ryan finds happiness in his life, Wilfred begs him to sacrifice it for a larger purpose.