Active drug use among HIV-infected persons is associated with poor adherence to highly active antiretroviral therapy (HAART) and suboptimal treatment outcomes. To understand adherence experiences among HIV-infected drug users, we conducted semistructured interviews with 15 participants in a randomized controlled trial evaluating the efficacy of directly observed HAART delivered in methadone maintenance clinics. Interviews were recorded, transcribed, and thematically analyzed. We identified negative and positive psychological themes associated with both drug use and adherence. Participants described tension between negative feelings (denial, shame, and perceived isolation) and positive feelings (acceptance, motivation, empowerment, and perceived connectedness), and they associated this tension with their own drug using and adherence behaviors. Sustained antiretroviral therapy adherence may require increased emphasis on understanding the psychological experience of HIV-infected drug users.