Tissue engineering utilizes the expertise within the fields of materials science, biology, chemistry, transplantation medicine, and engineering to design materials that can temporarily serve in a structural and/or functional capacity while a defect is regenerated. Of prominence in the realm of regenerative medicine is the issue of bone disease and degeneration, particularly among an increasingly aging population. Traditional methods for bone and joint replacement enjoy increasing success, but restoration of native tissue architecture remains the ideal. Toward this goal, the design of a tissue equivalent that can integrate with native bone must take into account the characteristics of this unique tissue. Firstly, the extracellular matrix of bone is a hierarchical, heterogeneous material that has features with sizes that range from the nanoscale to the macroscale. Secondly, there is synergy between these features that gives rise to a composite material with defined nano-, micro-, and macrophases. Understanding the role of these phases should lead to improved materials to aid bone regeneration. Emulating the structure of bone is difficult; nevertheless, researchers are developing nanocomposite materials that take us one step closer to attaining the mechanical and biological properties of bone. This article discusses the role of nanoscale parameters and interactions in bone and presents a few examples of how engineered nanocomposites attempt to mimic the hierarchical structure of bone in order to achieve tissue regeneration rather than repair.