Individuals with HIV/AIDS have disproportionately high depression and smoking prevalence rates. Smokers with HIV/AIDS are more susceptible to opportunistic infections, smoking-related illnesses, and mortality. African Americans (AAs) comprise nearly half of newly diagnosed HIV+ cases. We examined the relationship among smoking, depression, and gender in un- or under-insured AA patients (N = 289) at an urban community HIV/AIDS clinic in the southeastern US. Approximately 33% met criteria for a depressive disorder and 37% endorsed current smoking status. Men were more likely than women to be current smokers and depressed participants were more likely to smoke than non-depressed participants. Women had significantly higher rates of depression compared to men. Both depression and male gender independently predicted current smoking status. Depression and smoking are likely to co-occur in HIV/AIDS patients; however, standard smoking cessation interventions often exclude smokers with comorbid psychiatric and/or medical illnesses. Interventions addressing these comorbidities are warranted.