Nonadherence to combination antiretroviral (ARV) therapies (cART) is highly prevalent and significantly increases the risk of adverse human immunodeficiency virus (HIV) disease outcomes. The current study evaluated the hypothesis that prospective memory-a dissociable aspect of episodic memory describing the ability to execute a future intention-plays an important role in successful cART adherence. Seventy-nine individuals with HIV infection who were prescribed at least one ARV medication underwent a comprehensive neuropsychological and neuromedical evaluation prior to completing a 1-month observation of their cART adherence as measured by electronic medication monitoring. Nonadherent individuals (n = 31) demonstrated significantly poorer prospective memory functioning as compared to adherent persons (n = 48), particularly on an index of time-based ProM (i.e., elevated loss of time errors). Deficits in time-based prospective memory were independently predictive of cART nonadherence, even after considering the possible influence of established predictors of adherence, such as general cognitive impairment (e.g., retrospective learning and memory) and psychiatric comorbidity (e.g., depression). These findings extend a nascent literature showing that impairment in time-based prospective memory significantly increases the risk of medication nonadherence and therefore may guide the development of novel strategies for intervention. (JINS, 2009, 15, 42-52.).