Citrulline is an amino acid that is a common molecule in intermediary metabolism. The small intestine releases large amount of citrulline that is an end product of the intestinal glutamine metabolism. Moreover, citrulline can also be synthesized from arginine. NOSs are an important sources of citrulline. The activity of the intestinal enzymes that catabolize citrulline is very low. Therefore, citrulline can not be used in situ, and it is released into circulation. Citrulline is mainly taken up and metabolized by the kidneys. The plasma concentration of citrulline reflects difference between intestinal production and its metabolism by the kidney. Citrulline is a good marker of the functional state of intestine and kidneys. Citrulline level could be used to estimate the degree of renal damage, to detect acute and chronic renal failure. Citrulline concentration is increased in mild renal failure without any changes in uremia and creatininemia. Citrulline level is a surrogate marker for the NO synthesis. It may be also used as a marker of metabolic disorders and for estimation of the severity of heart failure.