We define regenerative engineering as a convergence of advanced materials science, stem cell science, physics, developmental biology, and clinical translation. Stem cells play an important role. Work in the area of musculoskeletal tissue regeneration has focused on a number of paradigms. Polymer and polymer-ceramic systems can be utilized for the regeneration of bone. Direct induction can be controlled through material characteristics. Through the use of inducerons, small molecules fostering induction, the design of regeneration-inducing materials can be realized. We believe the medicinal use of stem cells will be of critical importance in the design of next generation systems answering grand challenges to musculoskeletal regeneration.