Clinical experience since decades and numerous retro- and, recently, also prospective studies clearly demonstrate that prophylactic treatment, albeit much more expensive, is superior to on-demand treatment regardless if outcome focus on number of joint- or life-threatening bleeds or arthropathy, evaluated by X-ray or MRI, or quality of life measured by general or hemophilia specific instruments. Optimal prophylactic treatment should be started early (primary prophylaxis) but various opinions exist on the dose and dose interval, depending on the objective of treatment in the individual patient which in turn is usually dependent on the resources in the health care system. Secondary prophylaxis, started later in childhood or in adults is beneficial but less cost-effective. This review covers proof of concept of primary prophylaxis in children and secondary prophylaxis in adults, comparisons between prophylaxis and on demand treatment as well as outcome measurers, health economics and future trends of prophylactic treatment of hemophilia.