OBJECTIVE: To examine perceived discrimination and substance use among Latino high school students. METHODS: Latino 9(th) graders (N = 1332) completed self-report measures of perceived discrimination and substance use behavior. RESULTS: Perceived discrimination was associated with lifetime use measures of smoking (OR = 1.73, P < 0.01), alcohol (OR = 1.53, P < 0.01), marijuana (OR = 1.70, P < 0.01), and inhalants (OR = 1.50, P < 0.05); and past 30 day measures of smoking (OR = 2.54, P < 0.01), alcohol (OR = 1.63, P < 0.01), marijuana (OR = 1.95, P < 0.01), and inhalants (OR = 1.64, P < 0.01), and binge drinking (OR = 1.84, P < 0.01). CONCLUSIONS: Latino adolescents who have higher perceptions of discrimination are at risk for substance use. Interventions to help Latino adolescents cope with feelings of discrimination may be a useful addition to substance use prevention programs.