Hemophilia A and B are rare inherited bleeding disorders characterized by the deficiency of coagulation factor VIII (FVIII) or factor IX (FIX). While the history of hemophilia dates back to the 2nd century AD, a modern description of hemophilia appeared only at the beginning of the 19th century. The discovery of “antihemophilic globulin” in the middle of the 20th century paved the way to the production of cryoprecipitate and then of FVIII and FIX concentrates. Barring the tragic consequences on the hemophilia community of the transmission of blood-borne viruses by nonvirus inactivated factor concentrates during the 1970s and 1980s, plasma-derived first and recombinant products later revolutionized the treatment of hemophilia through the widespread adoption of home treatment and prophylaxis regimens, which dramatically improved the quality of life and life expectancy of persons with hemophilia during the past decade. This article briefly reviews the most important stages of the management of hemophilia from the past century up to the present days.