The association of depressive symptoms, neurocognitive impairment, and adherence to highly active antiretroviral therapy (HAART) was evaluated in 135 HIV-infected persons. Thirty percent reported nonadherence to HAART. Depressive symptoms (assessed with the Montgomery-Asberg Depression Rating Scale) and neurocognitive impairment (assessed with a neuropsychological test battery) were documented in 24% and 12%, respectively, of the study participants. Nonadherence to HAART was independently associated with worse depression rating scale scores (odds ratio=1.05, 95% confidence interval [CI]=1.00-1.10), acquisition of HIV through injection of drugs (odds ratio=2.59, 95% CI=1.05-6.39), and complaints about impairment of sexual activity (odds ratio=6.62, 95% CI=1.16-37.6). The presence of depressive symptoms, but not neurocognitive impairment, was associated with nonadherence.