OBJECTIVES: To conduct a systematic review of the literature to examine the interrelationship between mental health and treatment outcomes in low-income and middle-income settings; to update the work of Collins et al. (2006). DESIGN: Systematic review of peer-reviewed articles that examined one of the following: the effects of mental disorders (including cognitive impairment) upon engagement with treatment and/or adherence; their influence upon HIV-related clinical outcomes; and the impact of interventions for mental disorder. METHODS: Articles about mental health and HIV/AIDS were included if they were published after 2005 and addressed one of the areas of interest described above. Systematic methods were used for searching, screening, and data extraction. Studies employing quantitative measures of exposures and outcomes wherein all participants had a diagnosis of HIV/AIDS were included. RESULTS: This review found ample and moderately consistent evidence that adverse mental health and alcohol consumption are associated with reduced adherence. Variation in measurement and the relative paucity of work meant that interpretation of studies examining engagement with care and other clinical outcomes was difficult. Evidence on the efficacy and effectiveness of mental health interventions in low-income and middle-income settings was very limited. CONCLUSION: This review suggests that psychosocial factors, namely, depression and alcohol may have adverse effects upon HIV-related outcomes. However, further large, high-quality studies examining outcomes other than adherence are needed. There is also an urgent need for randomized controlled trials of interventions for mental disorder and a need to investigate their impact upon HIV-related outcomes.