Still a major problem in orthopedic and trauma surgery is the delayed healing or the non-union of long bone fractures. Demographic data reveal that due to the steadily rising age of the population, complications with the musculoskeletal system will increase during the next years. Bone morphogenetic proteins (BMPs) have successfully been applied in clinic for the treatment of delayed healing and non-unions. The broad difference concerning the indication, timing of treatment, dosage and application technique of BMPs calls for the need to perform further prospective studies in order to standardize the treatment and furthermore optimize the procedures or even develop new therapeutic strategies. For example, the application technique may be improved and in some cases injectable BMP preparations could be of use. Also the coating of implants with growth factors might be valuable in order to stimulate bone healing and to prevent delayed healing or non-union. This article tries to discuss some of the open questions, however can and will not reflect the absolute standard of care. To make the BMP treatment a standard of care, more clinical data and long time experiences are necessary. The intramedullary application of BMP in combination with autologous or allogenic bone grafts or bone substitutes after debridement and stabilization with implants seems to be an adequate procedure for treatment of atrophic non-unions. However, the total number of patients is too small to draw final conclusions. Further clinical studies need to be performed in the future.