The Alcohol and Drug Abuse Research Unit (ADARU) was established at the South African Medical Research Council (MRC) at the beginning of 2001, although its origins lie in the activities of the Centre for Epidemiological Research in Southern Africa and other MRC entities. Initial challenges included attracting external funding, recruiting new staff, developing the skills of junior staff, publishing in international journals and building national and international collaborative networks. ADARU currently comprises a core staff of 33 members who work on 22 projects spanning substance use epidemiology and associated consequences, intervention studies with at-risk populations and services research. A large component of this portfolio focuses on the link between alcohol and other drug use and human immunodeficiency virus (HIV) risk behaviour, with funding from the US Centers for Disease Control and Prevention. Junior staff members are encouraged to develop independent research interests and pursue PhD studies. Research outputs, such as the 20 papers that were published in 2010 and the 35 conference presentations from that year, form an important part of the unit's research translation activities. We engage actively with policy processes at the local, provincial, national and international levels, and have given particular attention to alcohol policy in recent years. The paper includes an analysis of major challenges currently facing the unit and how we are attempting to address them. It ends with some thoughts on what the unit intends doing to enhance the quality of its research, the capacity of its staff and its international standing.