In the past 50 years, the lifespan of an individual affected with severe hemophilia A has increased from a mere 20 years to near that of the general unaffected population. These advances are the result of and parallel advances in the development and manufacture of replacement therapies. We are now poised to witness further technologic leaps with the development of longer-lasting replacement therapies, some of which are likely to be approved for market shortly. Prophylactic therapy is currently the standard of care for young children with severe hemophilia A, yet requires frequent infusion to achieve optimal results. Longer-lasting products will transform our ability to deliver prophylaxis, especially in very young children. Longer-lasting replacement therapies will require changes to our current treatment plans including those for acute bleeding, prophylaxis, surgical interventions, and even perhaps immunotolerance induction. Ongoing observation will be required to determine the full clinical impact of this new class of products.