The anemia from which sickle cell (SS) anemia derives its name is broadly categorized as an uncompensated hemolytic anemia, in which a markedly shortened overall red cell (RBC) survival (increased rate of RBC destruction) is insufficiently balanced by the increase in production (erythropoiesis) to maintain normal levels of total RBCs and hemoglobin (Hb) concentrations. Although reduced RBC survival is usually considered primary in SS, both the intrinsic features of Hb S and its secondary effects result in a submaximal erythropoietic response, thereby contributing to the anemia. The following discussion considers the various components of hemolysis and erythropoiesis in this disease in the “steady state,” that is, in the absence of acute complicating factors.