This study examines gender differences in patterns of the co-occurrence of alcohol abuse and depression in youth. Data were from 1,458 youth (ages 9-17) randomly selected from the community. The child and one parent/guardian in each household were interviewed regarding childhood psychopathology, alcohol and drug use, and a wide array of risk factors. The findings showed that: (1) alcohol abuse/dependence was associated with elevated rates of depression in youth; (2) comorbidity between depression and alcohol use/abuse could be partially explained by shared risk factors; and (3) gender differences were found in the patterns of comorbidity. After controlling for other factors, the relationship between depression and alcohol abuse/dependence was no longer significant for girls, but it remained significant for boys. Among girls, however, cigarette smoking emerged as significantly related to depression. In the prevention of substance abuse and the treatment of depressive and addictive disorders, comorbidity of alcohol abuse and depression should be taken into account. Other clinical and policy implications are also discussed.