Skeletal muscle denervation is a complex clinical problem that still lacks a comprehensive solution. Previous studies have suggested that prolonged periods of denervation lead to a decline in the muscle stem cell population, negatively affecting the ability of muscle to regenerate following reinnervation. Recent advances in the understanding of muscle stem cell biology, along with new techniques that increase the ability to identify and manipulate these cells, provide an opportunity to definitively address the impact of muscle stem cells in recovery from denervation and their potential role in treatment.