Because of the rising numbers of patients affected by osteoarthritis (OA), management decisions on how to minimize pain and improve function in OA patients are important. Intra-articular hyaluronic acid (IAHA) knee injections have become a common treatment in the management of knee OA. In an editorial appearing in the 2007 National Knowledge Week on Osteoarthritis: National Health Service Evidence, four questions were asked about the clinical use of IAHA treatment for OA: 1) Who is the ideal candidate for HA viscosupplementation? 2) Do the mechanical and biological effects differ in importance in different stages of the disease? 3) What is the ideal dose in early- and late-stage OA? 4) Can the biological effect be delivered by means other than injection? These key issues are addressed. On the basis of results from several systemic reviews and meta-analyses, we conclude that IAHA knee injections in patients with knee OA result in modest improvements when measured by validated outcomes.