Osteoarthritis (OA) is the most common cause of localized or generalized joint pain in adults. OA is a condition that represents a complex of interactive degradative and reparative processes in the cartilage and bone with secondary inflammatory changes, particularly in the synovium. Although there is no known cure for OA, the treatment designed for the individual patients can reduce pain, maintain joint mobility, and limit the functional impairment. Guidelines for the treatment of OA include patient education and physical and occupational therapy. Weight loss has been shown to slow the progression of disease and to relieve symptoms in obese patients with OA of the knee. While low-impact exercise is beneficial, the adverse effects of high-impact and high-intensity activitiesy on the aggravation of OA have been documented. Most drug therapies with drugs are targeted to specific symptomsatic response. It is certainly worthwhile to initiate a trial of acetaminophen, known to be beneficial in OA patients with mild to moderate pain, on the basis of the risk-to-benefit ratio and cost. However, previous studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a better efficacy. The COX-2-specific inhibitors appear to be better tolerated, with a lower incidence of GI side effects, than comparator nonselective NSAIDs. However, the potential cardiovascular thrombotic events of these medications are considerable in the patients with hypertension or coronary artery disease. Although a number of agents are on the horizon, including glucosamine, chondroitin, diacerein, S-Adenosyl-L-Methionine, and hyaluronan, no agent has been shown to have a disease-modifying OA drug (DMOAD) effect at this time.