This article describes three community-based research projects that are designed to enhance the effectiveness of real-world adolescent substance abuse treatment and prevention, and presents preliminary study results from each. The first project is examining statewide public sector practitioner interest in and implementation of contingency management in treating adolescent substance abuse. The second project is integrating the Community Reinforcement Approach for adults into Multisystemic Therapy (MST) programs for use with substance-abusing caregivers. The third project is integrating Reinforcement-Based Therapy for adults with MST for child abuse and neglect in the treatment of families with co-occurring child maltreatment and caregiver substance abuse. Each project highlights the complexity of using the evidence base in the treatment of substance abuse, and the potential to improve outcomes for challenging clinical populations in real world practice settings.