Protein intake has been recognized as a modulator of renal function for over half a century. This review analyzes the renal response induced by changes in habitual protein intake and with acute amino acid infusion or a meat meal in humans and animals. The pattern and magnitude of changes in GFR and creatinine clearance are examined along with a discussion of the effect of the variability of these measurements among individuals and populations on the interpretation of clinical studies. Potential mechanisms of protein-induced changes in GFR and creatinine clearance are examined, including changes in the hormonal milieu, glomerular hemodynamics, and other intrarenal processes. Habitual dietary protein consumption varies significantly with respect to age, gender, and lean body mass--factors that are well known to influence GFR. This correlation raises the possibility that (1) variation in dietary protein intake may account, at least in part, for the differences in renal function among individuals; and (2) the level of protein intake should be assessed in defining the normal range of renal function.