Depression is highly prevalent among HIV-positive individuals and has been identified as an important predictor of suboptimal adherence to highly active antiretroviral treatment (HAART). To date, however, researchers have not adequately examined how depression influences adherence among depressed HIV-positive patients. The aim of our study was to explore the process by which depression interacts with other factors relevant to medication adherence decision making to influence adherence to HAART. We used principles of grounded theory to guide our methods. We conducted interviews with 21 HIV-positive individuals diagnosed with comorbid depressive disorders. Results indicated that depression, HIV-related cues, and health and self-care beliefs combined to influence coping strategies. Coping strategies, in turn, predicted whether participants were able to adhere to HAART. These findings can be used by practitioners to broaden the scope of factors they consider when treating depressed patients who might be at risk for nonadherence.