There are several important mechanisms by which renal prostaglandins modulate renal salt and water excretion. The role of endogenous renal prostaglandins in facilitating urinary sodium excretion and the individual nephron segments that are affected by renal prostaglandins are reviewed. The role of the administration of nonsteroidal anti-inflammatory agents on the kidney's ability to excrete salt and water both physiologically and clinically is summarized. The potential role for endogenous prostaglandins to antagonize the effect of antidiuretic hormone and to alter renal water excretion is also described. The clinical consequences of taking nonsteroidal anti-inflammatory drugs in terms of hyperkalemia, sodium retention with associated edema, and possible hyponatremia are all discussed. Although these clinical consequences are quite uncommon statistically, there are certain subsets of patients for whom additional concern is important.