Objective: The objective of the present article is to review and discuss Familias Unidas, an empirically supported, family-based, culturally specific drug abuse and HIV prevention intervention for Hispanic immigrant adolescents and their families. Method: The authors focus on engagement and retention as well as on intervention delivery. Conclusions: The present article serves as a guide for social workers and mental health practitioners in carrying out effective family-based adolescent substance use and HIV preventive interventions. Recommendations for and challenges to implementing the intervention in practice-based settings are discussed. (Contains 1 table.)