Advances in cancer screening and treatment have improved survival after a diagnosis of cancer. As the number of cancer survivors as well as their overall life-expectancy increases, investigations of health-related quality of life (HRQOL) are critical in understanding the factors that promote the optimal experience over the course of survivorship. However, there is a dearth of information on determinants of HRQOL for African American cancer survivors as the vast majority of cohorts have been conducted predominantly among non-Hispanic Whites. In this review, we provide a review of the literature related to HRQOL in cancer survivors including those in African Americans. We then present a summary of published work from the Detroit Research on Cancer Survivors (ROCS) cohort, a population-based cohort of more than 5000 African American cancer survivors. Overall, Detroit ROCS has markedly advanced our understanding of the unique factors contributing to poorer HRQOL among African Americans with cancer. This work and future studies will help inform potential interventions to improve the long-term health of this patient population.