Public health literature indicates that psychosocial stress is an important contributor to chronic disease development. However, there is scant research on the health effects of stress for minority groups, who suffer from a high burden of chronic disease. This paper provides a review of studies that examine the relationship between psychosocial stress and chronic disease for 4th world indigenous groups and African Americans. A total of 50 associational and 15 intervention studies fit the inclusion criteria for this review. A range of chronic diseases, as well as harmful health behaviors, were associated with psychosocial stress for indigenous peoples and African Americans, with much stronger findings for mental rather than physical health outcomes. Several stress moderating factors were also identified and a small body of intervention research suggests that transcendental meditation and group-oriented stress management may be effective in reducing psychosocial stress and its effects for African Americans and 4th world indigenous groups respectively.