This article provides a review of the literature on the acculturation of Latino and African-American adolescents to traditional European-American cultural values, and the effect on their substance abusing behaviors. The review includes a critical analysis of studies that examine the effects of acculturation on the mental health and well-being of Latino adolescents. Recent findings documenting the association between acculturation and substance abuse among Latino adolescents are discussed. The article also examines the dearth of research on the role of acculturation in the substance-abusing behaviors of African-American adolescents. The authors assert that understanding the effects of acculturation on these behaviors could begin to explain why African-American adolescent substance abuse rates have been historically lower than those of European-American and Latino adolescents. Also included is an examination of research on the role of acculturation in treatment outcomes of Latino and African-American adolescents.