Knowledge of factors associated with medication adherence could help HIV clinicians to target persons in need of intervention, design these interventions, and help researchers to plan studies of adherence. This review summarizes the results of 20 studies investigating the issue of barriers to optimal highly active antiretroviral therapy (HAART) adherence. Only a few determinants were consistently associated with nonadherence. Symptoms and adverse drug effects, psychologic distress, lack of social or family support, complexity of the HAART regimen, low patient self-efficacy, and inconvenience of treatment were the factors most consistently associated with nonadherence. There were inconsistent findings regarding the relationship of adherence and the following variables: sociodemographic characteristics, substance abuse, depressive symptoms, quality of life, CD4+ cell count, knowledge and beliefs about treatment, patients' satisfaction with health care, and patient-provider relationship. A synthesis of findings relating various factors to adherence to HAART is difficult to reach because of several limitations of the existing body of research. These limitations concern the measurement of adherence, the assessment of correlates and predictors of adherence, the study population, and the study design.