Objective: To determine whether childhood-onset bipolar disorder (BP) is associated with an increased psychiatric family history compared with adolescent-onset BP. Method: Semistructured psychiatric interviews were conducted for 438 youth with BP spectrum disorders. To evaluate the effects of age at onset and psychiatric family history, the sample was divided into childhood-onset BP (age and BP onset less than 12 years; n = 192), adolescents with early-onset BP (age greater than or equal to 12 years and BP onset less than 12 years; n = 136), and adolescents with late-onset BP (age and BP onset greater than or equal to 12 years; n = 110). Lifetime family history of psychiatric illness was ascertained for first- and second-degree relatives through both direct interview of caretakers and the Family History Screen. Results: After significant demographic and clinical factors were controlled for, children and adolescents with childhood-onset BP showed higher percentages of positive first-degree family history for depression, anxiety, attention deficit/hyperactivity, conduct, and substance dependence disorders and suicidal behaviors compared with adolescents with late onset. Subjects with childhood-onset BP also showed elevated familial loading for depression and attention-deficit/hyperactive disorder in second-degree relatives. Conclusions: These data support a model that postulates a higher density of familial risk for a broad range of psychopathology in childhood-onset BP. (Contains 4 tables.)