The cause of pathological gambling (PG) is unknown. The current study was conducted to determine whether PG is familial, and to examine patterns of familial aggregation of psychiatric disorder. To that end, 31 case probands with DSM-IV PG and 31 control probands were recruited and interviewed regarding their first degree relatives (FDRs). Available and willing FDRs were directly interviewed with structured instruments of known reliability, and best estimate final diagnoses were blindly assigned for 193 case and 142 control relatives over age 18 years. The results were analyzed using logistic regression by the method of generalized estimating equations. The lifetime rates of PG and bany gambling disorderQ were significantly greater among the relatives of case probands (8.3% and 12.4%, respectively) than among the control relatives (2.1% and 3.5%, respectively) (OR=3.36 for bany gambling disorderQ). PG relatives also had significantly higher lifetime rates of alcohol disorders, bany substance use disorder,Q antisocial personality disorder (ASPD), and bany mental disorderQ. bAny gambling disorder,Q alcohol disorder, and bany substance use disorderQ remained significant after a conservative Bonferroni correction. Interestingly, PG families were significantly larger than control families. We conclude that gambling disorders are familial and co-aggregate with substance misuse. The data are also suggestive that PG co-aggregates with ASPD. Further research on the heritability of PG is warranted.