Unique issues in blood donation and blood transfusion regarding African Americans (AA) in the United States span the donation process, manufacturing of products, and hospital transfusion service. As AAs become a growing population, a constant supply of blood donated by AAs is necessary to support this growth. Nationally, AAs are underrepresented in blood collection, which may be secondary to AAs having higher rates of anemia and other deferrable conditions or unique motivators as well as other barriers to blood donation. When investigating blood transfusion practices, blood utilization for different races and ethnicities is unknown. AAs may receive more red blood cell (RBC) transfusions because they have a higher proportion of diseases that require transfusion. Patients with sickle cell disease are at increased risk of RBC alloimmunization likely due to the predominance of RBC units from white donors in the existing blood supply, but it is not known if all AA recipients experience increased alloimmunization rates compared with whites. In conclusion, there is a need to increase donation by AAs, which can only be achieved by conducting studies to understand racial differences in donor recruitment and to better understand blood utilization and adverse events as a factor of race and ethnicity.