The objective of osteoarthritis (OA) treatment is not only control of symptoms (i.e. reducing pain and improving function) but also to preserve joint structure and maintain quality of life. OA management remains challenging. Glucosamine and chondroitin are two compounds available for treatment of OA patients. Taken alone or in combination, they have a good safety profile and a variety of effects. In-vitro and in-vivo experiments have revealed that both compounds induced key intermediates in the OA pathophysiological process. Clinical trials, although providing conflicting and questionable results, report symptomatic and structure-modifying effects for both pharmaceutical-grade compounds. This review will discuss all these subjects and emphasize the importance of the quality of tested compounds for achieving high quality clinical trials.