In this study we examined the association of optimism and depressive symptoms with self-reported physical symptoms in 241 low-income, inner-city African American women with or without a chronic illness (HIV). Although optimism was not a unique predictor of self-reported physical symptoms over and above depressive symptoms, optimism interacted with depressive symptoms and health status. In the community sample, but not the chronically ill sample, optimism buffered the association between depressive symptoms and self-reported physical symptoms. Clinical implications and directions for future research are discussed.