Success of highly active antiretroviral therapies (HAART) relies on HIV-infected patients being able to adhere to complicated treatment regimens for extremely long periods of time. Four focus groups with patients taking antiretrovirals (N = 39) were conducted to: (1) determine what strategies facilitate successful adherence; (2) determine what barriers prevent adherence; and (3) investigate the health-care provider and patient relationship and how it may impact adherence. Quantitative and qualitative information was gathered. Participants were prescribed an average of 15 pills per day (M = 14.7, SD = 6.3, range 4 to 36). Findings from the quantitative data revealed that the three strategies used most often to aid adherence were: carrying special containers for medication; having a health-care provider explain or clarify medication requirements; and carrying food and water for adherence to special instructions. The most difficult barriers for patients were sleeping through dose time, problems in following special instructions, and changes in daily routines. From the qualitative data, four main categories of barriers and aids to adherence emerged: patient characteristics, the health-care provider-patient relationship, the health-care system, and issues related to the medication regimen. Barriers related to the health care provider-patient relationship included patient satisfaction with their provider, as well as quality of communication with the provider. In addition, health-care system barriers caused difficulty in maintaining adherence. Implications for patient as well as provider interventions are discussed.