Renal sympathetic denervation, a minimally invasive procedure targeting the ablation of renal sympathetic nerves to attenuate systemic sympathetic hyperactivity, has demonstrated therapeutic efficacy in cardiovascular diseases such as hypertension. Emerging evidence indicates that sympathetic overactivation serves as a critical pathophysiological driver in multiple disease states. Consequently, renal sympathetic denervation may hold promise as a novel therapeutic strategy for these conditions. This review synthesizes current clinical and preclinical findings to elucidate the mechanistic and clinical implications of renal sympathetic denervation across cardiovascular, respiratory, renal, and metabolic disorders.