The prevalence of HIV infection among injection drug users and other highly marginalized groups is a significant health issue in Canada. Vancouver’s Downtown Eastside (DTES) is particularly hard hit, with HIV prevalence rates estimated at 25 per cent. These high rates of HIV infection persist in spite of efforts to reduce HIV transmission through various prevention programs, harm reduction strategies, treatment facilities and community law enforcement. HIV prevention strategies and treatment therapies that are effective among other populations have not had the same success in the most vulnerable and marginalized members of society. As an HIV clinician and researcher in the DTES, Dr. Mark Tyndall’s research takes three streams: Observational Cohort Studies: Identifying trends in risk behaviors, drug use patterns, HlV/Hepatitis C rates, social changes, law enforcement initiatives, and the impact of harm reduction interventions on key health indicators; Antiretroviral Therapy: Developing and evaluating strategies and programs that enhance the uptake, delivery and sustainability of antiretroviral therapy to marginalized groups; and Clinical trials research: Advancing Vancouver as a centre for clinical trials research for the evaluation of candidate HIV vaccines and other novel therapies among marginalized groups. Together, Dr. Tyndall’s studies will allow for evidence-based decision-making and improved health outcomes for marginalized groups living with HIV in the DTES and other urban areas in BC.