Patient adherence to combination therapy is a critical component of successful treatment outcomes. While combination therapy is known to be effective in slowing disease progression, the long-term benefit of these therapies can only be sustained if resistant strains of HIV do not emerge. Among factors that can result in the emergence of resistance, non-adherence is perhaps the most amenable to intervention. To maximize intervention efforts, a program of research on adherence is needed. A prerequisite for progress in adherence research is a focused effort on developing reliable and valid methods for measuring adherence that are feasible for patients living with HIV/AIDS. If new adherence assessment procedures cannot be developed, it would be helpful if a consensus on measurement approaches could be achieved. This consensus might propose strategies for matching measurement approaches with research questions and recommendations for the use of multiple measures where appropriate. It is important that research continue to identify psychological, physiological, socio-cultural and environmental factors that are associated with non-adherence in various populations both in the developed and the developing world. Intervention programs that address these risk factors and promote adherence need to be developed and evaluated in controlled clinical trials. These programs will need to be tailored to different populations and cultural groups, and tested in both developed and developing countries where HIV therapies are being prescribed. The results of this research would significantly contribute to efforts to prevent virus breakthrough and, by doing so, assist persons living with HIV/AIDS in achieving the health benefits that the combination therapies offer.