Ozone therapy is used for its immunomodulatory, antioxidant, and analgesic properties in several fields. It can be useful in the rehabilitation of musculoskeletal disorders. Studies showed that O-O therapy can reduce pain and improve functioning in patients affected by low back pain and knee osteoarthritis. Only a few studies have been published about the efficacy of this treatment in upper limb disease. : The aim of this study is to investigate the use of ozone therapy in upper limb pathologies, evaluating its quantity, quality, and reported results in upper limb musculoskeletal disease, supraspinatus tendinopathy, shoulder impingement, adhesive capsulitis, chronic epicondylitis, and carpal tunnel syndrome. O-O reduces inflammation by stimulating anti-inflammatory cytokines and inactivating pro-inflammatory molecules, relieves pain by interacting with pain receptors and improving blood circulation, promotes the regeneration of damaged tissues by stimulating growth factors and improving vascularization, and, finally, activates endogenous antioxidant defense systems by protecting cells from oxidative damage. : A comprehensive search was conducted on PubMed and Scopus using the following MeSH terms: ozone therapy, infiltration joint, musculoskeletal disease, rehabilitation, upper limb, shoulder, wrist, hand, elbow, including English papers published in the last five years. : Five papers have been selected: four randomized controlled trials and one retrospective cohort study. The RCTs compared the effectiveness of intra-articular ozone injection with steroid injection alone or with other conservative treatments in shoulder diseases; one paper studied the effectiveness of ozone injection and orthoses in carpal tunnel syndrome compared to orthoses alone; one paper used ozone injections compared with steroid injection in patients with chronic lateral epicondylitis. A total of 218 patients were studied in these trials. : Ozone treatment seemed to improve pain and function as well as other therapies in upper limb musculoskeletal disease. However, the trials' protocols and the upper limb areas treated are different. Further studies are needed to define the effectiveness of ozone therapy in upper limb diseases in rehabilitation fields.