OBJECTIVE This study surveyed high school student drug users in urban areas of Mexico to describe use patterns and drug-related behaviors among adolescents and to develop predictor models of pathways to underage drug use. A National School Survey was conducted among high school students where data are provided by the State. Only urban sites were considered for this study (n = 40,521). Stratified two-stage cluster sampling was used; schools and groups within the schools were the sampling units. CONCLUSIONS Male adolescents who have worked the previous year, have high exposure within the family and are affiliated with drug using peers are at increased risk of becoming drug users and subject to depression and suicidal ideation as well as drug-related social problems.