Insulin has been shown to have anti-natriuretic actions in humans and animal models. Moreover, endogenous hyperinsulinemia and insulin infusion has been correlated to increased blood pressure in some models. In this review, we present the current state of understanding with regard to the regulation of the major renal sodium transporters by insulin in the kidney. Several groups, using primarily cell culture, have demonstrated that insulin can directly increase activity of the epithelial sodium channel (ENaC), the sodium phosphate cotransporter (NaPi-2), the sodium hydrogen exchanger (NHE3), and sodium potassium ATPase (Na-K-ATPase). We and others have demonstrated alterations in the expression at the protein level of many of these same proteins with insulin infusion or in hyperinsulinemic models. We also discuss how this regulation is perturbed in type I and type II diabetes mellitus. Finally, we discuss a potential role for regulation of insulin receptor signaling in the kidney in contributing to sodium balance and blood pressure.