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This secondary data analytic effort identified psychosocial predictors of adherence to antiretroviral therapies in middle-aged and older adults living with HIV/AIDS. The current study is needed because rates and predictors of adherence identified in research with younger samples of HIV-infected persons may not generalize to older populations. In particular, this study examined relationships between depression, pain, and self-reported cognitive functioning with intentional and unintentional nonadherence to medications in middle-aged and older adults with HIV disease. Depression significantly predicted adherence in this group in logistic multiple regression analyses; however, this association was less clear when escape-avoidant coping was included in the model. Pain and cognitive functioning showed no correlational relationship with medication adherence. Findings from this research can delineate rates of adherence in HIV-infected older adults and inform the conceptualization of interventions intended to optimize rates of adherence in this understudied population.