In the United States, phlebotomies are most often performed for reinfusion of blood to a designated or nondesignated recipient at a later time. These are known, respectively, as autologous or allogenic donations. For a few rare blood disorders, however, phlebotomy is performed as a medical intervention for disease management. These are referred to as therapeutic phlebotomies. Four classifications of blood disorders are discussed here for which symptoms and complications can be managed by the use of therapeutic phlebotomy. The article also offers considerations for setting up a therapeutic phlebotomy program.