Causes of the excess incidence rates of chronic kidney disease in the African American population have long been under study. Recently, polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) have been associated with nondiabetic kidney diseases in African- and European-derived populations. Risk variants in MYH9 contribute to approximately 70% of nondiabetic forms of ESRD in African Americans and 40 to 45% of all ESRD in this ethnic group, with lesser effects in European Americans. It is clear that MYH9 polymorphisms have a significant impact on the incidence rates of kidney disease in African Americans. This article describes the current spectrum of biopsy-proven MYH9-associated kidney diseases, along with potential effects of MYH9 on ethnic differences in clinical outcome. MYH9 risk variants exhibit the most impressive association with any common complex kidney disease yet identified.