This is a systematic review of eighty-two published studies investigating the impact of DSM-IV mental disorders on combination antiretroviral therapy (cART) adherence and persistence among persons living with HIV/AIDS (PLWHA). Sixty-two articles examined depression, with 58 % (N = 32/62) finding lower cART adherence and persistence. Seventeen articles examined one or more anxiety disorders, with the majority finding no association with cART adherence or persistence. Eighty percent of the studies that evaluated the impact of psychotic (N = 3), bipolar (N = 5) and personality disorders (N = 2) on cART adherence and persistence also found no association. Seven out of the nine studies (78 %) evaluating the impact of antidepressant treatment (ADT) on cART adherence found improvement. Adherence and depression measurements varied significantly in studies; common research measurements would improve data harmonization. More research specifically addressing the impact of other mental disorders besides depression on cART adherence and RCTs evaluating ADT on cART adherence are also needed.