A significant number of adults with HIV in the USA do not maintain adherence to highly active antiretroviral therapy (HAART) at adequate levels. Although traditional cognitive behavioral interventions have shown promise in promoting HAART adherence, acceptance-based behavior therapy (ABBT) may be particularly useful in this population. ABBT has the potential to overcome common avoidance-based barriers associated with poor adherence, including denial of various illness-related factors and avoidance of stigmatization. We describe the rationale for promoting psychological and behavioral acceptance in HIV-positive populations; outline an ABBT to promote HAART adherence targeting primary care patients from urban, minority, low socioeconomic backgrounds; and report preliminary qualitative observations of treatment feasibility and acceptability.