Fracture-healing is a complex, highly organized biological process that leads to the restoration of skeletal integrity by the regeneration of bone. This unique property differentiates bone from other tissues and is essential for skeletal health, homeostasis, and survival. Although fracture-healing is one of the most consistent and reliable reparative responses of human tissue, its impairment or failure can lead to devastating clinical consequences. Conversely, a comprehensive understanding of the basic science of fracture-healing may reveal some of the most well-kept secrets of nature, providing clinicians and scientists with new paths for investigation and leading to advanced therapies for the treatment of skeletal injuries and diseases. This article summarizes the key discussion points of the 2007 American Academy of Orthopaedic Surgeons (AAOS) Research Symposium entitled "Fracture Repair: Challenges and Opportunities." The major goals of this meeting were (1) to identify the unmet needs and research directions for basic, translational, and clinical research in fracture-healing so as to guide the scientific community, and (2) to provide critical feedback to the National Institutes of Health (NIH) to impact their long-range planning and priority-setting processes.