Fracture healing is a biologically optimized process. Despite the expectation of unimpaired healing, approximately 5% to 10% of the 7.9 million fractures sustained annually in the United States have difficulty achieving union. Not only does this cause morbidity for patients, but also enormous healthcare and socioeconomic costs. Hence, there is a compelling need to find novel therapies to enhance fracture healing. In this article, we summarize current data on therapies to enhance skeletal healing and review their suggested biologic functions, proposed clinical applications, and known efficacies.