The prevention of bleeding by prophylactic factor replacement is the recommended approach for the treatment of severe hemophilia. Prophylaxis should be individualized to provide the best clinical benefit to each patient. Therefore, a pharmacokinetic approach is crucial. Areas covered: This review aims to concisely describe the basic principles of pharmacokinetics of FVIII, the role of population pharmacokinetic, the available different recombinant FVIII concentrates and the new extended half-life FVIII molecules with possible improvement in hemophilia A treatment. Expert opinion: Pharmacokinetic is a useful tool to predict the outcome of replacement therapy, even though a large inter-individual variability exists, becauseof several factors: age, weight, von Willebrand factor level, blood group, active bleed, presence of inhibitors to FVIII, FVIII concentrate. Among the different recombinant FVIII concentrates pharmacokinetic differences are minor and clinically not significant. The extended half-life FVIII products brings only moderate advances, as half life extension is limited to 1.5-1.8-fold in comparison to that of native FVIII. Thus, infusions could be done every fourth, rarely fifth day to ensure a safe through level and a significant benefit can be offered only to patients treated every other day or three times weekly.