Highly active antiretroviral therapy (HAART) has significantly decreased the morbidity and mortality of persons infected with HIV. The extent of the benefits, however, is not uniform, and certain factors including ethnicity, gender, baseline HIV viral load and CD4+ T lymphocyte count, adherence and intravenous drug abuse are associated with different immunological, virological and clinical outcomes. Mental health illness (MHI) and specifically depression may be associated with worse outcomes, although studies exploring the impact of MHI on HIV outcomes in both the pre-HAART and post-HAART eras have shown mixed results. The objective of the current paper is to review the available literature on the impact of MHI on HIV outcomes in the HAART era.