Small bowel disease encompasses a broad range of pathological states starting with functional disorders through inflammatory disease to morphological injury with possible intestine loss. Some of these conditions result in major loss of function presenting as intestinal failure. The term intestinal failure refers to a condition whereby the bowel is unable fulfil its basic function in the process of digestion and absorption of nutrients. Unlike other organs, where reliable laboratory markers of injury or failure are available, no such tests are currently on hand for the bowel. Determination of the plasma citrulline level is a reliable marker for assessing the mass of functional intestinal tissue. Citrulline is an amino acid formed almost exclusively in enterocytes and not present in food proteins. The liver has only a minimal effect on citrulline production. Eighty percent of citrulline is converted in the kidney to arginine. Its impaired renal clearance results in increased citrulline levels. Clinically relevant are decreased citrulline levels as they reflect a lack of functional mass of enterocytes. The aim of the present review is to summarize current knowledge and to define the value of determining plasma citrulline levels for the diagnosis of intestinal failure and, possibly, for monitoring the bowel function.