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The pathophysiology of hypertension, which affects over 1 billion individuals worldwide, involves the integration of the actions of multiple organ systems, including the kidney. The kidney, which governs sodium excretion via several mechanisms including pressure natriuresis and the actions of renal sodium transporters, is central to long term blood pressure regulation and the salt sensitivity of blood pressure. The impact of renal sodium handling and the salt sensitivity of blood pressure in health and hypertension is a critical public health issue owing to the excess of dietary salt consumed globally and the significant percentage of the global population exhibiting salt sensitivity. This review highlights recent advances that have provided new insight into the renal handling of sodium and the salt sensitivity of blood pressure, with a focus on genetic, inflammatory, dietary, sympathetic nervous system and oxidative stress mechanisms that influence renal sodium excretion. Increased understanding of the multiple integrated mechanisms that regulate the renal handling of sodium and the salt sensitivity of blood pressure has the potential to identify novel therapeutic targets and refine dietary guidelines designed to treat and prevent hypertension.