Prostate cancer incidence and mortality rates are remarkably higher in African-American men as compared to their European-Americans counterparts. Despite these recognitions, precise causes underlying such prevalent racial disparities remain poorly understood. Although socioeconomic factors could account for such differences up to a certain extent, it is now being increasingly realized that such disparity has a molecular basis. Indeed, several differences, including genetic polymorphism, gene mutations, epigenetic modifications, miRNAs alterations, etc., have been reported in malignant prostate tissues from patients of diverse racial backgrounds. Here, we attempt to provide a molecular perspective on prostate cancer racial disparities by gathering available information on these associated factors and discussing their potential significance in disproportionate incidence and clinical outcomes.