BACKGROUND: Electrical stimulation is commonly employed for activation of paralyzed muscles in patients with neurological diseases and injuries. However, there are differences in the treatment approaches that are possible for upper motor neuron and lower motor neuron injuries. METHODS: This narrative review synthesizes findings from preclinical studies and clinical reports published over the past decades. Key topics include stimulation parameters, muscle physiology under denervation, and outcomes of invasive and noninvasive interventions. The selection of sources was based on their relevance to denervated muscle stimulation in both experimental and therapeutic contexts. RESULTS: This review critically examined the physiological and therapeutic differences between indirect and direct stimulation of muscles in upper motor neuron and lower motor neuron injury situations. It then focused on the much less well-established field of stimulation of denervated muscle, where there remains a pressing need for new clinical approaches. We explained the rationale for stimulating denervated muscles and the practical difficulties encountered in doing so, describing the use of both invasive and noninvasive devices in animal experiments and clinical trials. We then discussed related research using artificial reinnervation for denervated muscle stimulation and suggested directions for future exploration in this dynamic field. CONCLUSION: Stimulation of denervated muscle remains a promising but underdeveloped area. Electrical stimulation of denervated muscle can preserve muscle mass and potentially restore function. However, its clinical adoption has been limited by the exceptionally high stimulation thresholds required, which are approximately one thousand times higher than those for indirect muscle stimulation via intact lower motor neurons. These demands lead to significant challenges including discomfort, limited specificity due to the need for large electrodes, and the risk of tissue damage. Artificial reinnervation may offer a promising solution by enabling the use of conventional low-energy stimulation techniques. Additionally, the application of stimulation in free muscle transfers may further expand therapeutic options in this area.