Recent advances in biology, medicine, and engineering have led to the discovery of new therapeutic agents and novel materials for the repair of large bone defects caused by trauma, congenital defects, or bone tumors. These repair strategies often utilize degradable polymeric scaffolds for the controlled localized delivery of bioactive molecules to stimulate bone ingrowth as the scaffold degrades. Polymer composition, hydrophobicity, crystallinity, and degradability will affect the rate of drug release from these scaffolds, as well as the rate of tissue ingrowth. Accordingly, this chapter examines the wide range of synthetic degradable polymers utilized for osteogenic drug delivery. Additionally, the therapeutic proteins involved in bone formation and in the stimulation of osteoblasts, osteoclasts, and progenitor cells are reviewed to direct attention to the many critical issues influencing effective scaffold design for bone repair.