There is no "gold standard" for the assessment of adherence to HIV/AIDS medications. Similarly, there is no single optimal tool that enhances adherence to HIV/AIDS treatment regimens. This article presents a model that provides a heuristic for selecting adherence assessment approaches and intervention strategies based on the purpose for which each is to be used. First, a broad distinction is made between research and clinical settings. Second, with each of these settings, the selection of assessments and interventions is based on the extent to which the focus is on HIV/AIDS in general or on adherence in particular. Examples applying the model are provided. Finally, new dimensions are discussed for expanding the model, with particular attention to applying the model to the resource-limited settings that are so important in efforts to reduce the morbidity and mortality associated with the global threat of HIV/AIDS.