Adolescent substance use is one of today's most important social concerns, with Latino youth exhibiting the highest overall rates of substance use. Recognizing the particular importance of family connection and support for families from Mexican backgrounds, the current study seeks to examine how family obligation values and family assistance behaviors may be a source of protection or risk for substance use among Mexican-American adolescents. Three hundred and eighty-five adolescents (51% female) from Mexican backgrounds completed a questionnaire and daily diary for 14 consecutive days. Results suggest that family obligation values are protective, relating to lower substance use, due, in part, to the links with less association with deviant peers and increased adolescent disclosure. In contrast, family assistance behaviors are a source of risk within high parent-child conflict homes, relating to higher levels of substance use. These findings suggest that cultural values are protective against substance use, but the translation of these values into behaviors can be a risk factor depending upon the relational context of the family.