Recent editorials, conferences and clinical practice articles have discussed providers' concerns and practices regarding prescribing antiretroviral combination therapy for HIV. We aimed to deepen our understanding of these largely anecdotal reports and of the challenges facing experienced HIV clinicians today using qualitative methodology. Eight focus groups using a structured discussion guide were conducted. Data were analyzed by constant comparative analysis and open codes. Participants were a diverse group of 23 physicians, eight nurse practitioners and four physician assistants with significant experience providing care to HIV-seropositive patients in various San Francisco Bay Area health care settings. The following major themes emerged from the data: (1) providers expressed new optimism about helping HIV-seropositive patients live; (2) the main factors affecting providers' decisions about when to start combination therapy were the risks versus benefits of delaying therapy, and patients' health status, readiness to adhere and treatment preferences; (3) providers lacked resources to prepare patients to begin therapy and enhance adherence; (4) providers varied regarding assessment of adherence; and (5) providers were anxious about making decisions under conditions of uncertainty and were concerned about patient health outcomes. We concluded that experienced HIV clinicians were hopeful and excited about their increasing ability to help patients. This hope, however, was tempered by scepticism about the future and by their daily struggles to make treatment decisions under conditions of great uncertainty. Without access to adjunct supports or a multidisciplinary team, providers may not be able to optimally assess and enhance antiretroviral medication adherence.