Context Psychiatric symptoms including depression are common among people living with HIV/AIDS (PLWHA), and antidepressant medications have been shown to reduce depressive symptoms and also enhance antiretroviral (ARV) adherence in this population. Objective Because these benefits have not been studied among PLWHA using other psychotropic (PSY) medications in addition to antidepressants, we examined the impact of adherence to a diverse range of PSY medications (including antidepressants, mood stabilizers, and anti-psychotic medications) on depressive symptoms and ARV adherence in PLWA. Design Participants for this cohort study were recruited through physician outpatient clinics. Depressive symptoms were assessed monthly using a 10-item version of the Center for Epidemiological Studies – Depression (CES-D) scale; PSY and ARV medication adherence were assessed using monthly unannounced telephone pill count assessments across a three-month period. Setting A general community-based, healthcare setting was utilized for the study. Participants Of the 353 PLWHA we identified on stable ARV medications, we were able to maintain contact with 324 (92%) across a 3-month period (227 men; 97 women). Mean age of this convenience sample was 45 years and 90% were African-American. Intervention None. Main Outcome Measure Mean ARV adherence across a 3-month study period. Results The results showed that greater depressive symptoms were associated with lower ARV adherence among our sample of PLWHA. Greater adherence to PSY medications regardless of medication class was positively related to higher ARV adherence. We also found that greater adherence to PSY medications significantly reduced the negative association between depressive symptoms and ARV medication adherence among PLWHA. Conclusions The results of this study point to the need for screening and treatment of depressive symptoms and also further study of the impact of multiple PSY medications regimens on health outcomes among PLWHA.