The regeneration of bone remains an elusive yet important goal in the field of orthopaedic surgery. Despite its limitations, autogenous cancellous bone grafting continues to the most effective means by which bone healing is enhanced clinically. Biosynthetic bone grafts currently are being developed as an alternative to autogenous bone grafting. These grafts generally contain one or more of three critical components: (1) osteoprogenitor cells; (2) an osteoconductive matrix; and (3) osteoinductive growth factors. The importance of each of these components based on preclinical data supports their use in biosynthetic bone grafts. The use of growth factors such as bone morphogenetic proteins, transforming growth factor, platelet derived growth factor, and fibroblastic growth factor is reviewed in preclinical long bone defect and spinal fusion models. The use of bone marrow in preclinical and clinical settings is presented with specific emphasis given to the use of bone marrow as a source of osteoprogenitor cells and how the use of these cells can be enhanced with the use of bone morphogenetic protein-2. These data support the concept that although products that contain only one of the three key components of a bone graft may regenerate bone successfully, composites of the three key components will be more successful clinically.