The authors identified longitudinal relationships between early risk and protective factors from the domains of family, personality, and peer influences and later tobacco use in Puerto Rican adolescents living in New York. Aspects of the ethnic minority experience as moderators of familial risk and protective factors were investigated. Participants were 282 female and 276 male Puerto Rican adolescents interviewed twice, 5 years apart. The authors used hierarchical regression analyses to identify a model with direct and indirect paths. Family, personality, peer, and early smoking domains were directly related to later adolescent smoking. Partial mediation occurred. The authors identified risk-protective and protective-protective interactions between variables from the ethnic minority experience and family domains. Interventions to reduce smoking among Puerto Rican adolescents should focus on multiple contexts, including aspects of the ethnic minority experience.