Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electro-magnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the shoulder including the rotator cuff tendons, glenohumeral articular cartilage, glenoid labrum, the joint capsule, and bone. Promising and established treatment modalities include hyaluronic acid (HA); platelet-rich plasma (PRP) and platelet rich concentrates (PRC); bone marrow aspirate (BMA) comprising mesenchymal stromal cells (MSCs alternatively termed medicinal signaling cells and frequently, misleadingly labelled "mesenchymal stem cells"); MSC harvested from adipose, umbilical, or placental sources; factors including vascular endothelial growth factors (VEGF), basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGFβ), bone morphogenic protein (BMP), and matrix metalloproteinases (MMPs); prolotherapy; pulsed electromagnetic field therapy; microfracture and other marrow-stimulation techniques; biologic resurfacing using acellular dermal allografts, allograft Achilles tendons, allograft lateral menisci, fascia lata autografts, and porcine xenografts; osteochondral autograft or allograft); and autologous chondrocyte implantation (ACI). Studies involving hyaluronic acid, platelet rich plasma, and medicinal signaling cells of various origin tissues have shown mixed results to-date as isolated treatments and as surgical adjuncts. Despite varied results thus far, there is great potential for improved efficacy with refinement of current techniques and translation of burgeoning preclinical work. LEVEL OF EVIDENCE: Level V, expert opinion.