The aim of this paper is to perform a critical review of the effectiveness of interventions for the purpose of enhancing adherence to antiretroviral therapy. The overall evaluation indicates that research is in its early stages. Although pilot studies provide support for the feasibility of their protocols, and preliminary results also suggest their capacity to improve adherence, only three major trials have reported significant improvement in adherence. The issues that will have to be addressed by future studies include: (a) the need for a theoretical and empirical understanding of the phenomena; (b) adoption of a format that fits the attributes of the population; (c) the use of multiple strategies involving key providers; (d) a concise and precise schedule governing the frequency and intensity of the intervention; (e) a careful selection of direct outcome; and (f) appropriate time measurement. In sum, greater efforts to design and evaluate interventions are needed to lead to an increase in adherence and improvement in treatment effectiveness.