The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends intra-articular (IA) hyaluronic acid (HA) for management of knee osteoarthritis (OA) as second-line treatment in patients who remain symptomatic despite use of non-steroidal anti-inflammatory drugs (NSAIDs). This recommendation is based upon accumulating evidence that IA HA provides a significant benefit in knee OA. There is good evidence that IA HA injections reduce pain and increase function in knee OA, and the benefits are long-lasting as compared with IA corticosteroids. Evidence from real-life studies of repeat courses of IA HA demonstrates an improvement in pain or function lasting up to 40 months (12 months after the last injection cycle), a reduction in use of concomitant analgesia by up to 50%, and suggests that there may be a delay in the need for total knee replacement (TKR) of around 2 years. The clinical benefit of IA HA on knee OA may be 2-fold: (i) mechanical viscosupplementation of the joint (allowing lubrication and shock absorption) and (ii) the re-establishment of joint homeostasis through induction of endogenous HA production, which continues long after the exogenous injection has left the joint. The magnitude of the clinical effect may be different for different HA products, but this has not been proven so far and requires further investigation. IA HA injections are generally considered to be safe, although a slightly higher number of cases of local reactions and post-injection non-septic arthritis has been reported with high molecular weight cross-linked HAs. The use of IA HA in knee OA patients with mild-moderate disease, and for more severe patients wishing to delay TKR surgery, is recommended by the ESCEO task force. Further investigation into the OA patient types most likely to benefit from IA HA is warranted. Viscosupplementation with IA HA is a safe and effective component of the multi-modal management of knee OA.