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Skeletal muscle is a fundamental organ in the generation of force and movement, the regulation of whole-body metabolism, and the provision of resiliency. Indeed, physical medicine and rehabilitation is recognized for optimizing skeletal muscle health in the context of aging (sarcopenia) and disease (cachexia). Exercise is, and will remain, the cornerstone of therapies to improve skeletal muscle health. However, there are now a number of promising biologic and small molecule interventions currently under development to rejuvenate skeletal muscle, including myostatin inhibitors, selective androgen receptor modulators, and an activator of the fast skeletal muscle troponin complex. The opportunities for skeletal muscle-based regenerative therapies and a selection of emerging pharmacologic interventions are discussed in this review.