The study explored the relationship between HIV medication adherence and alcohol, cognitive, social and affective factors in 272 persons with alcohol problems. Alcohol and cognitive factors significantly differentiated those who did and did not adhere. Specifically, adherence confidence and number of drinks emerged as subfactors driving the associations to adherence. Among those who were less than perfectly adherent (n = 154), only alcohol factors predicted levels of nonadherence. Cognitive factors play a role in understanding some of the differences between those who do and do not adhere to their HIV medications, but they do not differentiate among levels of nonadherence.