This chapter provides an overview of the application of synthetic polymeric biomaterials in musculoskeletal regenerative and reconstructive medicine with selected examples. Hydrogels capable of cell and growth factor delivery were assessed for injectable cartilage tissue engineering. Injectable composite scaffolds incorporating bone morphogenetic protein-2 (BMP-2) were developed to regenerate critical-sized defects in a rat femoral defect model. Advanced scaffold design was achieved by computer aided stereolithography. Nerve tubes with multiple parallel channels were investigated as guidance scaffolds for peripheral nerve and spinal cord regeneration. All of these demonstrated the versatility of synthetic polymers as multifunctional, interactive, and biodegradable bioscaffolds with virtually unlimited possibility for performance optimization through polymer and surface chemistry modification and physical manipulation.