To present nationally representative data on lifetime prevalence and comorbidity of pathological gambling with other psychiatric disorders and to evaluate sex differences in the strength of the comorbid associations. Data were derived from a large national sample of the United States. Some 43,093 household and group quarters residents age 18 years and older participated in the 2001-2002 survey. Prevalence and associations of lifetime pathological gambling and other lifetime psychiatric disorders are presented. The diagnostic interview was the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. Fifteen symptom items operationalized the 10 pathological gambling criteria. The lifetime prevalence rate of pathological gambling was 0.42%. Almost three quarters (73.2%) of pathological gamblers had an alcohol use disorder, 38.1% had a drug use disorder, 60.4% had nicotine dependence, 49.6% had a mood disorder, 41.3% had an anxiety disorder, and 60.8% had a personality disorder. A large majority of the associations between pathological gambling and substance use, mood, anxiety, and personality disorders were overwhelmingly positive and significant (p .05). Pathological gambling is highly comorbid with substance use, mood, anxiety, and personality disorders, suggesting that treatment for one condition should involve assessment and possible concomitant treatment for comorbid conditions.