PARP is a nuclear enzyme with a major function in the DNA damage response. PARP inhibitors (PARPi) have been developed for treating tumors harboring homologous recombination repair (HRR) defects that lead to a dependency on PARP. There are currently three PARPi approved for use in advanced prostate cancer (PCa), and several others are in clinical trials for this disease. Recent clinical trial results have reported differential efficacy based on the specific PARPi utilized as well as patient race. There is a racial disparity in PCa, where African American (AA) males are twice as likely to develop and die from the disease compared to European American (EA) males. Despite the disparity, there continues to be a lack of diversity in clinical trial cohorts for PCa. In this review, PARP nuclear functions, inhibition, and clinical relevance are explored through the lens of racial differences. This review will touch on the biological variations that have been explored thus far between AA and EA males with PCa to offer rationale for investigating PARPi response in the context of race at both the basic science and the clinical development levels.