Medication adherence is essential to successful treatment of HIV/AIDS. Maintaining high adherence will likely prove a major challenge in Africa -- just as it has in developed nations. Despite early reports suggesting that adherence would not pose a major barrier to treatment success, more recent research shows that adherence rates in Africa are quite variable and often poor. Given the large number of patients whose disease will progress if adherence is suboptimal, research is urgently needed to determine patient-level behavioral barriers to adherence and the most effective and appropriate methods for assessing adherence in African cohorts.