Rising rates of substance use among Hispanic youth, coupled with substantial growth of this minority group, merit grounds for concern. The process of assimilation is frequently examined in studies of Hispanic substance use and has been cited as a reason for higher rates of substance use by U.S.-born Hispanics, compared to their foreign-born peers. However, many previous studies use individual or unidimensional measures of assimilation, when this term is multifaceted, representing different concepts. The current study addresses this gap by testing the longitudinal effect of different assimilation processes (acculturation as well as structural, spatial, and straight-line assimilation), while simultaneously controlling for important familial and social risk and protective factors on the likelihood of alcohol use among U.S.-born Mexican and Mexican immigrant youth. Results indicate that, although alcohol use is higher among immigrant youth, assimilation measures do not predict alcohol use for immigrants or U.S.-born youth. We conclude that the effects of assimilation may vary by person and place, particularly in ethnic enclaves, and suggest the use of measures that incorporate cultural, personal, social, and environmental factors.