Annual sales of glucosamine as a neutraceutical for affecting cartilage in treatment of osteoarthritis are close to a billion dollars, but recent clinical studies have currently raised severe criticism regarding its functional value. Additional doubts can be raised by the knowledge of the well-defined cellular steps in glucosamine formation and production of glycosaminoglycans such as chondroitin. Glucosamine is produced in an activated state from glucose by essentially all cells for incorporation into glycosaminoglycans and glycoproteins, and there have been no reports of any deficiencies in its production under any conditions. Nevertheless, many investigations of glucosamine, using cells or tissues, have claimed effects on cartilage and chondroitin sulfate. The significance of these studies is questionable since they have invariably been with concentrations that were 10- to 1000-fold higher than has been found in human serum or plasma after glucosamine ingestion. Experiments with cells or tissues using glucosamine in the low concentrations found after ingestion need to be examined before any conclusions are drawn concerning its direct action on cartilage and its potential for modifying osteoarthritis.