The Dombrock blood group system (Do) consists of two antithetical antigens (Do(a) and Do(b)) and five antigens of high prevalence (Gy(a), Hy, Jo(a), DOYA, and DOMR). Do antigens are carried on the Dombrock glycoprotein, which is attached to the RBC membrane via glycosylphosphatidylinositol linkage. The gene (DO, ART4) encoding the Do glycoprotein, located on the short arm of chromosome 12, has been cloned and sequenced, allowing the molecular basis of the various Do phenotypes to be determined. Do(a) and Do(b) have a prevalence that makes them useful as genetic markers; however, the paucity of reliable anti-Do(a) and anti-Do(b) has prevented this potential from being realized. The ease with which these antigens can be predicted by analysis of DNA opens the door for such studies to be carried out. Anti-Do(a) and anti-Do(b) are rarely found as a single specificity, but they have been implicated in causing hemolytic transfusion reactions. This review is a synthesis of our current knowledge of he Dombrock blood group system.