Osteoarthritis (OA) is a common, chronic disease that most frequently affects the knees and is a major cause of disability in the elderly. It is characterized by progressive cartilage loss, accompanied by secondary changes such as osteophyte formation and calcium deposition. Inflammatory processes are also involved, leading to stiffness and pain, for which patients seek treatment. Conventional treatment includes analgesics or non-steroidal anti-inflammatory drugs, however life-style changes should also be recommended, such as weight reduction and specific exercises. Glucosamine and chondroitin, classed as over-the-counter supplements or nutraceuticals, are regularly self-administered by patients with OA. Both agents are produced endogenously in the human body and are essential components of cartilage. This review discusses the evidence that supports the use of these agents either alone or in combination for pain relief and as disease-modifying agents in OA.