The glucose substitutes (fructose, sorbitol, xylitol) have significant metabolic advantages in stress situations as compared to glucose. Side-effects are usually not to be expected if indications and dosage are carefully determined. The only contraindication for fructose and for sorbitol is hereditary fructose intolerance. However, this metabolic disease should be known to physicians who are involved in parenteral nutrition. Fructose intolerance might also be diagnosed by the metabolic alterations caused by fructose or by sorbitol administration in such patients. It was shown repeatedly during the last few decades that glucose formed in the liver during metabolism of glucose substitutes and delivered to the circulation is obviously metabolized without an increase in blood glucose concentration and without additional requirement of insulin. No explanation for this amazing, long-observed metabolic effect is known to date. These reproducible results should stimulate new investigations. Such effects should not be rejected or questioned because they do not fit into the hypotheses.