Approximately 500 million years ago, the Paleozoic era heralded an evolutionary marvel: the skeleton. Unique to this evolutionary development was the capacity for regeneration: the physiologic renewal of embryologically derived tissue. Many of the cellular and molecular components for bone regeneration have been identified (bone morphogenetic proteins), and their therapeutic manipulation will become common clinical practice. Moreover, synthetic materials produced in the laboratory and novel bone derivatives will be used to exploit the skeleton's capacity to regenerate and repair. The concept of repair may be viewed as the restoration of form and function to deficient osseous tissue. Materials that provoke repair can be categorized broadly as bone substitutes. In this review, bone substitutes are grouped into 2 categories, polymers and ceramics, and each is subclassified as biodegradable or nonbiodegradable. Examples of these materials are provided as well as some of their liabilities and virtues.