Types of alternative therapies used, demographic and medical data, coping (Billing and Moss Inventory of Coping with Illness Styles), social support (Irwing and Sarason Questionnaire), sense of personal control (Pearlin’s Mastery Scale), quality of life (Medical Outcome Study Scale), health beliefs and adherence rate were prospectively assessed in 118 HIV-infected patients receiving highly active antiretroviral therapy (HAART). Of 38% (45/118) of the patients that used alternative therapies, 56% (25/45) began using alternative therapies since the initiation of HAART. While Caucasian patients were more likely to use alternative therapies than all other patients, new users of alternative therapies were more likely to be African-American. Alternative therapy users reported less satisfaction with their emotional support and had greater psychological distress, but were more likely to use problem-focused coping. Patients that used alternative therapies were less likely to believe that HAART was beneficial. Physicians were unaware of patients’ alternative therapies in 67% of herbal therapy users, and in 100% of dietary supplement users. Adherence to antiretroviral therapy, CD4 count, and HIV-RNA level were neither predictive nor affected by alternative therapy use. Despite scepticism about the benefits of HAART, resorting to alternative therapies did not undermine adherence with antiretroviral therapy. Although able actively to cope with their illness, users of alternative therapies had greater psychological distress and were less satisfied with their emotional support. Interventions aimed at promoting psychological well-being and enhancing emotional support should be considered for these patients.