PubMed and Ovid Medline were searched to investigate the role of intramedullary nailing in the treatment of diaphyseal humeral non-union. Of 474 abstracts, 9 retrieved articles fulfilled our inclusion criteria and described management in 166 cases of humeral shaft non-union using several types of intramedullary nails. Union ranged from 40 to 100%; part of the variation could be explained by the quality index of the selected articles. Exchange nailing alone was not effective. Exposure of the fracture site and use of bone grafting were key to successful treatment. The total incidence of severe complications, including radial nerve damage, was very low. Thus, intramedullary nailing in the treatment of humeral shaft non-unions can lead to successful outcomes when associated with autologous bone grafting.