Mg++ is widely involved in human physiological processes that may play key roles in the generation and progression of diseases. Osteoarthritis (OA) is a complex joint disorder characterized by articular cartilage degradation, abnormal mineralization and inflammation. Magnesium deficiency is considered to be a major risk factor for OA development and progression. Magnesium deficiency is active in several pathways that have been implicated in OA, including increased inflammatory mediators, cartilage damage, defective chondrocyte biosynthesis, aberrant calcification and a weakened effect of analgesics. Abundant in vitro and in vivo evidence in animal models now suggests that the nutritional supplementation or local infiltration of Mg++ represent effective therapies for OA. The goal of this review is to summarize the current understanding of the role of Mg++ in OA with particular emphasis on the related molecular mechanisms involved in OA progression.