The increasing incidence of open tibial and femoral fractures causes great suffering by patients and is an enormous economic burden, necessitating improved treatment. The current treatment of these fractures is reviewed, as well as the evolving role of intramedullary nailing in this treatment. Intramedullary nailing seems to give better results than external fixation in Gustilo type I and II fractures, and is at least as good in type III. The introduction of the non-reamed interlocking intramedullary nail may bring about even better outcomes. Any improvements in treatment should be based on thorough understanding of the biology and biomechanics of the injury.