Osteoarthritis (OA) of the knee is a chronic and progressive disease that is the product of failure of the joint to repair cartilage breakdown and wear. This article reviews the physiologic properties and pathological changes in the synovial fluid that occur in patients with OA. Exogenous hyaluronic acid (HA) has analgesic, chondroprotective, and disease-modifying effects. Viscosupplements of HA are useful in the treatment of OA in conjunction with other methods of conservative treatment. Viscosupplementation may be better tolerated than oral medication, which can have significant side effects and drug interactions. Unlike other OA treatments, viscosupplements do not carry precautions for comorbidities, such as diabetes or cardiovascular disease. A number of HA viscosupplements are available for intra-articular injection in the treatment of knee OA. These supplements vary in molecular weight, dosage per injection, residence time in the joint, and number of injections required for treatment.