Advances in hemophilia management in the 20th century enabled effective and early treatment of joint and other bleeds typical of this disease, also in a home setting. Prophylaxis became available as the optimal approach to prevent hemophilic arthropathy and improve patients' quality of life. To increase treatment safety, lyophilized plasma-derived factor VIII and IX concentrates were subjected to numerous procedures designed to decrease the risk of transmission of known and unknown pathogens. During the following years, recombinant factor VIII and factor IX preparations were developed to completely eliminate the risk. Recombinant factor concentrates were extensively studied in terms of their therapeutic properties, safety, and immunogenicity. This article reviews the current knowledge on efficacy and safety of recombinant factors VIII and IX.