Nonsteroidal anti-inflammatory drugs (NSAIDs) are capable of inducing a variety of renal function abnormalities, particularly in high-risk patients with decreased renal blood perfusion who depend on prostaglandin synthesis to maintain normal renal function. Fluid retention is the most common NSAID-related renal complication, occurring to some degree in virtually all exposed individuals; however, clinically detectable edema occurs in less than 5% of patients and is readily reversible on discontinuation of the NSAID. Other electrolyte complications, notably hyperkalemia, are seen infrequently and occur in specific at-risk patients. The next most worrisome complication is acute deterioration of renal function, which occurs in high-risk patients and is also reversible. Nephrotic syndrome with interstitial nephritis is a rare problem of NSAID use and is reversible. Papillary necrosis is the only permanent complication of NSAIDs and is very rare. Altogether, these renal function abnormalities, with the exception of mild fluid retention, are clinically detectable in approximately 1% of exposed patients. Given the number of patients who take NSAIDs on a prescription or over-the-counter basis, the absolute number of at-risk patients is relatively large. Consequently, an appreciation for the risk factors and pathophysiology of NSAID-induced renal function abnormalities is required for optimal use of these drugs.