The discovery of bone morphogenetic proteins marks a major step forward in the understanding of bone physiology and in the development of advanced methods in skeletal surgery. The cornerstones for successful growth-factor therapy in skeletal surgery remain biomechanical stability and biological vitality of the bone providing an adequate environment for new bone formation. Knowledge of the biological characteristics, mechanisms of action, and methods of delivery of growth factors will become essential for skeletal surgeons. The current clinical application of bone morphogenetic proteins is safe and efficacious as a result of a well-regulated cascade of events leading to bone formation. Clinical trials have not yet determined whether different clinical indications each require a specific bone-tissue-engineering format or if a single pathway for stimulating bone-healing with growth factors is sufficient.