The focus of this review is on the role of the renal nerves in contributing to the sodium retention associated with cirrhosis, congestive heart failure, and nephrotic syndrome. With respect to these three disease state information is presented which indicates that conditions exist which would be predicted to activate the sympathetic nervous system. Consistent with this, indirect indices of increased peripheral and renal sympathetic nerve activity are observed in these diseases. Acute experiments have indicated that the renal nerves are influencing sodium excretion in these sodium-retaining disorders. The renal nerves have the capacity to influence tubular sodium transport, renal hemodynamics, and renal endocrine release, all of which may affect the renal handling of sodium. Experiments are discussed which have implicated all three mechanisms of action in cirrhosis and congestive heart failure. Despite the fact that studies are demonstrating an increasing importance of the renal nerves, experiments have not been conducted to definitively implicate the renal nerves as being responsible for the long-term sodium retention in these disease conditions.