Normal bone healing is a complex process that eventually restores original structure and function to the site of trauma. However, clinical circumstances such as nonunion, critical-sized defects, systemic bone disease, and fusion procedures have stimulated a search for ways to enhance this normal healing process. Biologics are an important part of this search and many, including bone marrow aspirate concentrate, demineralized bone matrix, platelet-rich plasma, bone morphogenic proteins, and platelet-derived growth factor, are currently in clinical use. Many others, including mesenchymal stem cells, parathyroid hormone, and Nel-like molecule-1 (NELL-1) will likely be in use in the future depending on the results of preclinical and clinical trials.