Hispanic adolescents represent a growing segment of the U.S. population. In addition to the typical stressors encountered during adolescence, Hispanic adolescents may experience acculturative stress, perceived discrimination, and conflicts with parents about acculturation, which can lead to maladaptive behaviors such as substance use. Personal cultural resources may help Hispanic youth cope with cultural stressors and avoid substance use, but little is known about how such factors affect decisions about substance use. In 2005, my research group began studying a group of Hispanic adolescents in Los Angeles. The participants completed surveys annually about cultural issues such as acculturation, ethnic identity, and perceived discrimination; family and peer relationships; and use of alcohol, tobacco, and marijuana. We found that Hispanic adolescents' perceptions that they were discriminated against put them at greater risk for substance use, and that Hispanic orientation protected the youth from substance use. The findings can inform the development of culturally relevant prevention interventions for Hispanic adolescents and emerging adults.