Gaylord “Greg” Focker and his wife Pam, daughter of retired CIA agent Jack, have five-year-old twins, Henry and Samantha.

Jack has heart problems and appoints Greg to the new head of the family, the “Godfocker”. However, he starts to have doubt about his decision, because he thinks Greg has an affair with Andi Garcia, a sexy pharmaceutical-company representative. This is not true, the impression is due to coincidences and drunkenness of Andi. Jack even suggests to Pam that it might be better to divorce Greg and resume her relationship with Kevin Rawley, her former fiancé. Greg and Pam are annoyed by this.