We explored the relation between 8 domains of Hispanic stress and alcohol use and frequency of use in a sample of Hispanic adolescents between 11 and 19 years old (N = 901). Independent t tests were used to compare means of domains of Hispanic stress between adolescents who reported alcohol use and those who reported no use. In addition, multinomial logistic regression was used to examine whether domains of Hispanic stress were related to alcohol use and whether the relation differed by gender and age. Multiple imputation was used to address missing data. In the analytic sample, 75.8% (n = 683) reported no use and 24.2% (n = 218) reported alcohol use during the previous 30 days. Higher mean Hispanic stress scores were observed among youths who reported alcohol use during the previous 30 days in 5 domains: acculturation gap, community and gang violence, family economic, discrimination, and family and drug-related stress. Increased community and gang violence, family and drug, and acculturative gap stress were found to be associated with some alcohol use categories beyond the effect of other domains. Few differences in the association between Hispanic stress and alcohol use by gender and age were observed. Study findings indicate that family and drug-related, community and gang violence, and acculturative gap stress domains are salient factors related to alcohol use among Hispanic adolescents, and their implications for prevention science are discussed.