This study investigates the relationship between discrimination and substance abuse among Latina/os, and further examines whether this relationship differs by gender and type of discrimination. Analyses focus on the Latina/o respondents (n = 1,039 men; n = 1,273 women) from the National Latino and Asian American Study carried out from 2002-2003. Outcomes were alcohol abuse and drug abuse measured using DSM-IV definitions and criteria. Additional covariates included immigrant characteristics and demographics. Analyses were completed using gender-stratified multinomial logistic regression. Men reported more discrimination (39.6% vs. 30.3%) and had higher prevalence of alcohol abuse (16.5% vs. 4.5%) and drug abuse (9.5% vs. 2.3%) than women. Discrimination was significantly associated with increased risk of alcohol abuse for women and increased risk of drug abuse for men. Men and women also varied in the types of discrimination (e.g., racial vs. gender) reported, and in the associations between these types of discrimination and substance abuse. These data indicate that discrimination is associated with different substance abuse outcomes between genders. Future research should consider the mechanisms that explain these differences.