Factor VIII or IX replacement in a prophylactic manner is utilized for many patients with moderate to severe hemophilia A or B. Studies have shown it to be effective in reducing or preventing degenerative joint disease in many but not all patients. However, many unanswered questions still exist and optimization of this expensive treatment regimen is needed. This paper recounts the current products that are available for use and explores the literature regarding different treatment regimens. It explores age at initiation, dose, interval between infusions, joint health outcomes, barriers to compliance and age at discontinuation of prophylaxis. Individualized treatment is recommended. Collaborative efforts are needed to improve outcomes for all persons with hemophilia.