Knowledge is limited regarding decision-making about antiretroviral treatment (ART) from the patient's perspective. This substudy of a longitudinal study of psychobiologic aspects of long-term survival, conducted in 2003, compares the rationales of HIV-positive individuals (n = 79) deciding to take or not to take ART. Inclusion criteria were HIV/AIDS symptoms, or CD4 nadir less than 350, or viral load greater than 55,000. Those not meeting any criteria for receiving ART (2/2003 U.S. DHHS treatment guidelines) were excluded. Diagnosis was on average 11 years ago; 36% were female, 42% African American, 28% Latino, 24% white, and 6% other. Qualitative content analysis of semistructured interviews identified 10 criteria for the decision to take or not to take ART: CD4/viral load counts (87%), quality of life (85%), knowledge/beliefs about resistance (66%), mind-body beliefs (65%), adverse effects of ART (59%), easy-to-take regimen (58%), spirituality/worldview (58%), drug resistance (41%), experience of HIV/AIDS symptoms (39%), and preference for complementary/alternative medicine (17%). Participants choosing not to take ART (27%) preferred complementary/alternative medicine (r = 0.43, p < 0.001)1, perceived a better quality of life without ART (r = 0.32, p < 0.004), and weighted avoidance of adverse effects of ART more heavily (r = 0.24, p < 0.030) than participants taking ART (73%). Demographic characteristics related to taking ART were having a partner (r = 0.31, p < 0.008) and having health insurance (r = 0.26, p < 0.040). Decisions to take or not to take ART depend not only on patient medical characteristics, but also on individual beliefs about ART, complementary/alternative medicine, spirituality, and mind-body connection. HIV-positive individuals declining treatment place more weight on alternative medicine, avoiding adverse effects and perceiving a better quality of life through not taking ART.