The development and introduction of recombinant factor VIII (rFVIII) concentrates nearly 20 years ago represented a major advance in the treatment of hemophilia A patients. Currently, first-, second- and third-generation rFVIII products are commercially available. Whereas first-generation rFVIII concentrates are stabilized with human albumin, second-generation rFVIII products contain sucrose instead of albumin in the final formulation. Finally, third-generation rFVIII products are manufactured without additional human or animal plasma proteins. The use of rFVIII concentrates has greatly improved the safety of replacement therapy in hemophilia A and virtually abolished the risk of blood-borne pathogen transmission. The remaining and most challenging aspect of hemophilia A management has now become the development of FVIII inhibitors. In this article we review the current knowledge on the commercially available rFVIII concentrates, analyzing their main characteristics. Moreover, results of the literature on their clinical hemostatic efficacy and safety are summarized.