Assessment of glomerular filtration rate (GFR) by common creatinine-based methods potentially is very inaccurate in patients with cirrhosis. Cirrhotic patients have several underlying conditions that contribute to falsely low serum creatinine concentrations, even in the presence of moderate to severe renal impairment, and often cause creatinine-based methods to overestimate true GFR. Such underlying conditions include decreased creatinine production secondary to decreased hepatic creatine synthesis, increased tubular creatinine secretion, and decreased skeletal muscle mass. These factors all contribute to serum creatinine concentrations that often do not accurately reflect renal function. Serum creatinine level, measured creatinine clearance, and calculated creatinine clearance may all significantly overestimate GFR; the degree of GFR overestimation was a median of 95% in published studies. Until more accurate methods of estimating GFR in cirrhotic patients are adequately validated, care should be exercised in the management of these patients because of the potential for severely impaired renal function, even in the face of normal serum creatinine concentrations.