General Background: The renal nervous system regulates kidney function through sympathetic and sensory neurons, impacting blood pressure and fluid balance. Specific Background: Renal nerve hyperactivity is linked to hypertension and metabolic disorders, prompting interest in renal denervation as a treatment. Knowledge Gap: The precise mechanisms by which renal nerves influence disease remain unclear, and clinical outcomes of renal denervation are inconsistent. Aims: This review explores renal nerve structure, neurotransmission, and functional roles in health and disease. Results: Sympathetic nerves release norepinephrine and co-transmitters, affecting vascular resistance and sodium handling, while sensory nerves modulate sympathetic output. Novelty: It integrates recent findings on renal neurophysiology, emphasizing afferent-sympathetic interactions. Implications: Advancing knowledge of renal nerves could refine treatments for hypertension and kidney disorders. Highlights: Renal nerve signaling controls blood pressure and kidney function through neurotransmitters like norepinephrine and ATP. Renal denervation therapy shows potential for treating hypertension but has inconsistent clinical outcomes. Afferent-sympathetic interaction plays a crucial role in kidney function and systemic homeostasis Keywords: Renal Nerves, Sympathetic Regulation, Hypertension, Neurotransmitters, Renal Denervation