The purpose of this study was to examine the associations of physical health stressors and coping resources with depressive symptoms among American Indian older adults age 50 years or older. The study used a convenience sample of 227 rural American Indian older adults. A hierarchical multiple regression tested three sets of predictors on depressive symptoms: (a) sociodemographics, (b) physical health stressors (functional disability and chronic medical conditions), and (c) coping resources (social support and spirituality). Most participants reported little difficulty in performing daily activities (e.g., eating, dressing, traveling, and managing money), while presenting over two types of chronic medical conditions. Depressive symptoms were predicted by higher scores on perceived social support and lower scores on functional disability; women and those having no health insurance also had higher levels of depressive symptoms. Findings suggest that social work practitioners should engage family and community support, advocate for access to adequate health care, and attend to women's unique circumstances and needs when working with American Indian older adults.