Objective: To examine perceived discrimination and substance use among Latino high school students. Methods: Latino 9th 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 less than 0.01), alcohol (OR=1.53, P less than 0.01), marijuana (OR=1.70, P less than 0.01), and inhalants (OR=1.50, P less than 0.05); and past 30 day measures of smoking (OR=2.54, P less than 0.01), alcohol (OR=1.63, P less than 0.01), marijuana (OR=1.95, P less than 0.01), and inhalants (OR=1.64, P less than 0.01), and binge drinking (OR=1.84, P less than 0.01). Conclusions: Latino adolescents who have higher perceptions of discrimination are at risk for substance use. Interventions to help Latino adolescent scope with feelings of discrimination may be a useful addition to substance use prevention programs.