Nonadherence to HIV-related medication regimens among drug-abusing patients decreases therapeutic effectiveness and may limit patient access to newer, highly active antiretroviral therapies (HAART). A number of factors have been associated with medication nonadherence; however, few studies have examined predictors of nonadherence specifically in HIV-positive drug abusers. In the current study, a comprehensive assessment battery was administered to 42 HIV-positive, injection drug users beginning methadone maintenance. HIV-related medication adherence was assessed weekly by self-report during the 4-week methadone stabilization phase. Thirty-six percent of patients reported less than 80% adherence to their medication regimen at entry into methadone. Medication adherence increased significantly during the 4-week stabilization phase. Significant zero-order correlations were found between nonadherence during stabilization and viral load, low educational attainment, depression, and neuropsychological tests of problem solving ability and cognitive flexibility. Independent predictors of nonadherence were low levels of education and poor emotional functioning. Implications for early intervention are discussed.