Osteonecrosis of the femoral head remains a devastating disease for young patients. As the normal process of bone formation, bone destruction, and fracture healing becomes more clearly understood, molecular agents--including cytokines, bone morphogenetic proteins, and angiogenic factors--will be identified as potential therapeutic agents for the treatment of osteonecrosis. As the pathology of osteonecrosis and repair of osteonecrotic lesions becomes clear, the potential combination of these molecular factors to influence the outcome of the disease in its repair process should become evident. With the myriad of agents and combinations of agents which may be beneficial in the treatment of osteonecrosis, a reproducible animal model is urgently needed to determine which of these combinations is most effective. Despite the lack of an animal model, progress in the use of cytokines for osteonecrosis treatment in conjunction with traditional treatment methods is possible in human subjects. This is due to the extremely low incidence of adverse reactions when these cytokines are used locally in nanogram to microgram quantities.