A consensus definition of malnutrition does not exist. We define“clinically relevant malnutrition”as the state of altered nutritional status that adversely affects clinical outcome. Over four years we have attempted to delineate a clinically applicable and validated nutritional assessment approach. This was accomplished through multiple clinical studies on a large number of surgical patients many of whom were seriously ill. Although an initial prospective study in 64 patients confirmed the relationship between certain nutritional markers and outcome, we found that 97% of patients had at least one abnormality, while 35% had three or more abnormalities, clearly documenting the imprecision in unselected battery testing. In a subsequent retrospective analysis of 161 patients, serum albumin (Alb), serum transferrin (TFN), triceps skinfold (TSF), and skin test reactivity (DH) proved to be the best markers of clinically relevant malnutrition and their relative quantitative importance is embodied in our Prognostic Nutritional Index (PNI), where PNI (% risk) = 158 - 16.6 (Alb) - 0.78 (TSF) - 0.20 (TFN) - 5.8 (DH). In numerous prospective studies of different patient groups, a large percentage of which were critically ill, the PNI has been shown to be a reliable nutritional assessment tool for diagnosing clinically relevant malnutrition. Furthermore, we have shown that seriously malnourished patients classified by the PNI will clinically benefit from preoperative nutritional support. The relevance of baseline and serial nutritional assessment to the nutritional care of the critically ill patient is discussed.