OBJECTIVE: To review the pharmacology and pharmacokinetics of glucosamine and critically evaluate currently available literature regarding its safety and efficacy. DATA SOURCE: A MEDLINE search was conducted between January 1965 and May 1997. Key words used in the search were osteoarthritis, osteoarthrosis, gonarthrosis, and glucosamine. In addition, references cited in articles obtained from the MEDLINE search were reviewed for additional literature. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for inclusion in the review. Articles were excluded from critical evaluation for lack of randomization, lack of a control group, 30 or fewer study participants, inconsistent treatment regimen, incomplete dosing information, or incomplete reporting of results. DATA SYNTHESIS: Osteoarthritis affects approximately 12% of the US population; the incidence increases with increasing age. Currently used pharmacologic treatments, including acetaminophen and nonsteroidal antiinflammatory drugs, do not slow or reverse the degenerative process in osteoarthritis. Glucosamine has recently received a great deal of attention from the public as a potential treatment of osteoarthritis, prompting healthcare professionals to investigate its clinical usefulness and potential for adverse effects. The drug has been proposed to stop and possibly reverse the degenerative process in osteoarthritis. Following absorption of an oral dose, glucosamine is incorporated into plasma proteins during first-pass metabolism, resulting in 26% bioavailability. Unbound glucosamine is concentrated in the articular cartilage. Each of the three critically evaluated studies reported a decrease in the symptoms of osteoarthritis (e.g., decreased Lequesne index, decreased pain severity, increased range of motion) for the glucosamine group, which was greater than that obtained in the control group. Flaws in study design, however, prevent the use of these results in modifying current clinical practice. Reported short-term adverse effects include mild gastrointestinal problems, drowsiness, skin reactions, and headache. CONCLUSIONS: Improvement in the symptoms of osteoarthritis associated with the use of glucosamine has been observed in clinical trials; however, those trials have flaws in design and data analysis. Further research needs to be conducted before glucosamine can be recommended as a treatment for osteoarthritis.