Optimal adherence to antiretroviral medications is critical to the effective long-term management of HIV infection. Although prospective memory (ProM; i.e., “remembering to remember”) has long been theorized to play an important role in medication adherence, no prior studies have evaluated whether HIV-associated ProM impairment possesses unique predictive value in this regard. Results from this study demonstrate a robust association between ProM impairment and self-reported medication management in 87 HIV-infected persons currently prescribed antiretroviral medications. Specifically, more frequent ProM complaints and performance deficits on both laboratory and semi-naturalistic ProM tasks were all independently related to poorer self-reported medication management. A series of hierarchical regression analyses revealed that HIV-associated ProM impairment accounted for a significant amount of variance in self-reported medication management beyond that which was explained by other factors known to predict nonadherence, including mood disorders, psychosocial variables, environmental structure, and deficits on a traditional battery of neuropsychological tests. Overall, these findings support the hypothesis that ProM captures a unique and largely untapped aspect of cognition that is germane to optimal medication adherence. The potential benefits of individualized remediation strategies that are informed by conceptual models of ProM and specifically target medication adherence warrant further exploration.