Orthobiologics encompass numerous substances that are naturally found in the human body including platelet-rich plasma (PRP), isolated growth factors, and cell therapy approaches to theoretically optimize and improve the healing of cartilage, fractures, and injured muscles, tendons, and ligaments.PRP is an autologous derivative of whole blood generated by centrifugation and is perhaps the most widely used orthobiologic treatment modality. Despite a vast amount of literature on its use in osteoarthritis as well as in tendon and ligament pathology, clinical efficacy results remain mixed, partly as a result of insufficient reporting of experimental details or exact compositions of PRP formulations used.Mesenchymal stromal cells (MSCs) can be isolated from a variety of tissues, with the most common being bone marrow aspirate concentrate. Similar to PRP, clinical results in orthopaedics with MSCs have been highly variable, with the quality and concentration of MSCs being highly contingent on the site of procurement and the techniques of harvesting and preparation.Advances in novel orthobiologics, therapeutic targets, and customized orthobiologic therapy will undoubtedly continue to burgeon, with some early promising results from studies targeting fibrosis and senescence.