Serum creatinine is widely interpreted as a measure only of renal function; however, the serum level reflects not only renal excretion, but also the generation, intake, and metabolism of creatinine. In this review, we demonstrate that serum creatinine does not provide an adequate estimate of glomerular filtration rate (GFR), and contrary to recent teachings, that the slope of the reciprocal of serum creatinine vs time does not permit an accurate assessment of the rate of progression of renal disease. In clinical investigation, it is essential to utilize more accurate and sensitive measures of renal function to estimate GFR and progression. As effective treatments for progressive renal diseases are discovered, it will also be necessary to employ these measurements in clinical practice.