Synthetic bone replacement materials are now widely used in orthopedics. However, to date, replication of trabecular bone structure and mechanical competence has proved elusive. Maximization of bone tissue attachment to replacement materials requires a highly organized porous structure for tissue integration and a template for assembly, combined with structural properties analogous to living bone. Natural structural biomaterials provide an abundant source of novel bone replacements. Animal skeletons have been designed through optimization by natural selection to physically support and physiologically maintain diverse tissue types encompassing a variety of functions. These skeletons possess structural properties that provide support for the complete reconstruction and regeneration of ectodermal, mesodermal, and bone tissues derived from animal and human and are thus suited to a diversity of tissue engineering applications. Increased understanding of biomineralization has initiated developments in biomimetic synthesis with the generation of synthetic biomimetic materials fabricated according to biological principles and processes of self-assembly and self-organization. The synthesis of complex inorganic forms, which mimic natural structures, offers exciting avenues for the chemical construction of macrostructures and a new generation of biologically and structurally related bone analogs for tissue engineering.