Intraarticular injections of hyaluronic acid have been advocated for treatment of symptomatic knee osteoarthritis. Appropriate indications and favorable patient response factors, such as radiographic disease severity and age, are not clearly defined for this therapy. The current review of 80 knees with symptomatic osteoarthritis treated with hyaluronic acid revealed that approximately 2/3 of treated knees received 2/3 relief of pain. Hyaluronic acid treatment is not appropriate for all patients with knee osteoarthritis. Overall, less than 50% of treated knees achieved satisfactory results, and only 35% reported increased activity. Twenty-two patients (28% of knees; 22 knees) underwent surgery within 7 months of their index injection, suggesting an inadequate response to treatment. The treatment is not without complication because 11 patients (15% of knees; 12 knees) experienced adverse reactions, including one case of septic arthritis. The authors recommend intraarticular hyaluronic acid only for patients with symptoms and significant surgical risk factors and for patients with mild radiographic disease in whom conservative treatment has failed (physical therapy, weight loss, nonsteroidal antiinflammatory medication, and intraarticular steroid injection). It is inadvisable to treat patients with a complete collapse of joint space or bone loss with intraarticular hyaluronic acid, given their poor clinical response.