A number of diseases are treated by passive administration of human proteins. Human coagulation factor VIII (FVIII) is one such protein which is administered to hemophilia A patients in order to manage and treat hemorrhagic incidences. This mode of therapy suffers from the side effect of generating anti-FVIII antibodies (inhibitors) which neutralizes the function of the infused FVIII. At a time when efficient viral screening procedures are at place, development of inhibitors poses the greatest threat to such a therapy. Various predisposing factors, both patient and product-related, are responsible for the development of inhibitory antibodies. A proper understanding of these "risk-factors" would eventually help to better design therapeutic regimen to tackle hemophilia A.