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The development of therapeutic strategies for the treatment of hemophilia A has been a long-lasting issue since the initial identification of the disease in the early 19th century and has involved several major steps to reach contemporary treatment. The current replacement therapy involving intravenous infusion of plasmatic or recombinant factor VIII (FVIII) has been efficient to control bleeding episodes of patients with hemophilia A. Nonetheless, replacement therapy requires frequent infusions to maintain values of FVIII above the threshold of efficacy and represents a serious burden that significantly impacts the patient's quality of life. The recent half-life extension technologies have permitted the development of a first generation of long-acting FVIII variants with improved circulating survival. These molecules, which are now in clinical phase III studies or have already received food and drug administration (FDA) approval for therapeutic use will allow a reduction in the frequency of infusion and lighten the treatment of hemophilia A. However, the half-life extension of FVIII was not as efficient as initially expected, particularly with regard to the results obtained with other therapeutic molecules. To overcome these limitations inherent to the nature of FVIII biology, several bypassing therapies independent of the FVIII molecule are currently in development. These emerging approaches exploit the modulation of the coagulation/anticoagulation balance taking place in the hemostatic process to compensate for the FVIII deficiency. In this review, we recount the history of hemophilia A treatment up to the recent emerging therapies, with particular focus on infusion-based strategies.