Pain represents a significant source of morbidity, function loss, and decreased quality of life among people living with HIV. The present study examined the associations among pain, pain treatment, and ARV adherence among indigent, HIV-positive substance abusers. Participants were recruited via targeted sampling strategies, and completed a one-time computer-assisted personal interview. ANOVA and chi-square tests were used to analyze differences in demographics, health and psychological status, health behaviors, by pain and pain treatment status; a multivariate logistic regression model was constructed to examine the contribution of pain/treatment status to recent ARV adherence. Results indicated that those with untreated pain had lower odds of achieving gold-standard 95% ARV adherence as compared to the pain-free and treated pain groups; higher substance dependence symptoms were also associated with significantly lower odds of 95% ARV adherence. Findings suggest that pain management is critical to the health of people living with HIV, specifically those with high levels of co-morbid health and psychological problems. The prevalence of untreated pain was elevated among this group, and contributed to reduced ARV adherence. Providers of clinical care to disadvantaged HIV-positive patients should emphasize routine assessment and appropriate treatment of pain in order to provide comprehensive HIV care.