We define Regenerative Engineering as the Convergence of Advanced Materials Science, Stem Cell Science, Physics, Developmental Biology, and Clinical Translation for the regeneration of complex tissues, organs and organ systems. Biomaterials play a centrally important role. Work in the area of musculoskeletal tissue regeneration has focused on a number of biomaterial technologies. Polymeric nanofiber systems create the prospect for biomimetics that recapitulate connective tissue ultrastructure allowing for the design of biomechanically functional matrices, or next generation matrices that create a niche for stem cell activity. Polymer and polymer-ceramic systems can be utilized for the regeneration of bone. Through the use of inducerons, small molecules fostering induction, the design of regeneration-inducing materials can be realized. Hybrid matrices possessing micro- and nano-architecture can create advantageous systems for regeneration, while the use of classic principles of materials science and engineering can lead to the development of three dimensional systems suitable for functional regeneration of tissues of the knee. Through convergence of a number of technologies, with advanced materials science playing an important role, we believe the prospect of engaging future grand challenges is possible.