The authors examined the incidence of significant life events during the year prior to the onset of panic disorder and its relationship to childhood and family history of anxiety difficulties, comorbidity, and the course of illness in 223 panic patients followed in a naturalistic study of panic disorder. Similar to previous reports, antecedent negative life events occurred in the majority (80%) of patients. Patients with a childhood history of anxiety and comorbid adulthood major depression were more likely to report an antecedent, stressful life event. Antecedent events were not linked with comorbid, adulthood anxiety disorders or a family history of anxiety difficulties. Despite its associations with childhood anxiety pathology and adulthood major depression, the presence of an identifiable antecedent at the onset of panic disorder was not associated with the subsequent severity or course of the disorder.