Sometime ago, Glucosamine emerged as a natural supplement for arthritis patients that not only relieves arthritis symptoms, but also maintains joint health. However, when it comes to actually rebuilding cartilage, Glucosamine is far more effective with some assistance from Chondroitin, MSM, and Omega-3. Perhaps the most important aspect of glucosamine and chondroitin sulfate supplements is that they are thought to help slow or prevent the degeneration of joint cartilage, the underlying cause of osteoarthritis pain. Glucosamine and chondroitin sulfate dietary supplements may also help alleviate existing joint pain. Unfortunately, damage to cartilage is not readily repaired by the body. The surgery is generally performed in young adults who have a tear in the cartilage that surrounds the knee as a result of sports injury and is not effective in patients with widespread cartilage degeneration, or osteoarthritis. To evaluate the current evidence that support or disprove the use of glucosamine and chondroitin in the treatment of patients with osteoarthritis is explored. Besides the common OA therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the treatment with chondroprotective, such as glucosamine sulfate, chondroitin sulfate, hyaluronic acid, collagen hydrolysate, or nutrients, such as antioxidants and omega-3 fatty acids is a promising therapeutic approach. Numerous clinical studies have demonstrated that the targeted administration of selected micronutrients leads to a more effective reduction of OA symptoms, with less adverse events. We considered only studies with high level of evidence. The study included analysis of randomized controlled trials that included at least 40 patients in each intervention group, meta-analyzes and systematic reviews. Considering the best evidences until now, the use of glucosamine and chondroitin does not provide clinical relevant benefits to patients with osteoarthritis of the knee or hip (Level I of evidence and grade A of recommendation). Further trials with adequate technology are necessaries to elucidate this question.