OBJECTIVE: To characterize the usefulness of glucosamine sulfate in the treatment of patients with osteoarthritis (OA). DATA SOURCES AND STUDY SELECTION: Pertinent citations were identified via a MEDLINE search (January 1975–March 1997). Only trials available in the English language involving human subjects, OA, and glucosamine sulfate were selected for review. DATA SYNTHESIS: OA is the most common form of arthritis and represents a major cause of morbidity and disability in the elderly. The main symptom of OA is pain and most of the commonly prescribed medications (e.g, acetaminophen, nonsteroidal antiinflammatory drugs) have been targeted at relieving the pain. Some of these medications have serious adverse effects and do not necessarily change the natural course of the disease. Glucosamine sulfate, a nutritional supplement, has recently emerged as an alternative treatment option for patients with OA. The beneficial effects of this chondroprotective agent have been reported to reverse or at least stop the progression of the disease without inducing serious adverse effects. Limited data from short-term human trials suggest that glucosamine sulfate administered orally, intravenously, intramuscularly, and intraarticularly may produce a gradual and progressive reduction in joint pain and tenderness, as well as improved range of motion and walking speed. Results of the trials have also shown that glucosamine has produced consistent benefits (>50% overall improvement in symptom scores) in patients with OA and that, in some cases, it may be equal or superior to ibuprofen in controlling symptoms. CONCLUSIONS: There is evidence that glucosamine sulfate may provide pain relief, reduce tenderness, and improve mobility in patients with OA. Most of the current data, however, are derived from the European and Asian literature and there are no studies supporting the use of this agent in the US. The studies published to date have been done in small numbers of patients; adequate long-term trials examining the safety, efficacy, and optimal dosage requirements of glucosamine sulfate are lacking. Most of the available clinical data are difficult to interpret due to serious deficiencies in study design. Furthermore, studies evaluating the appropriate place of glucosamine sulfate in the therapeutic armamentarium of OA remain to be done.