During the past century, orthopaedic surgery has made major advances in many diseases and now has satisfactory treatments available to restore function for most diseases and injuries. However, one problem area that has not advanced as rapidly is osteonecrosis. Despite many years of basic and clinical research, minimal progress has been made in the understanding and treatment of this disease. The barriers to progress and potential solutions that might lead to breakthroughs will be explored and presented. Promising therapeutic pathways will be debated.