The identification and characterization of stem cells is introducing a paradigm shift in the field of orthopaedic surgery. Whereas in the past, diseased tissue was replaced with allograft material, current trends in research revolve around regenerating damaged tissue. Muscle-derived stem cells have an application in regeneration of articular cartilage, bone, and skeletal muscle. These postnatal (ie, adult) stem cells can be readily isolated via muscle biopsy. They can display long-term proliferation, high self-renewal, and multipotent differentiation. They also can be genetically modified to secrete growth factors important to tissue healing, thereby functioning as implantable, long-lasting reservoirs for these molecules. Taken together, this evidence suggests that muscle-derived stem cells are well suited for gene therapy and tissue engineering applications for the musculoskeletal system. Effective implementation of even just a few applications of muscle-derived stem cell-based tissue engineering has the potential to revolutionize the way certain musculoskeletal diseases are managed.