Platelet-rich plasma (PRP) has been generating considerable attention as an intra-articular treatment to alleviate the symptoms of osteoarthritis. Activated platelets release a host of soluble mediators such as growth factors and cytokines, thereby inducing complex interactions that vary across tissues within the joint. In vivo, PRP may promote chondrocyte proliferation and differentiation. The available data are somewhat conflicting regarding potential effects on synovial cells and angiogenesis modulation. PRP probably exerts an early anti-inflammatory effect, which may be chiefly mediated by inhibition of the NF-κB pathway, a hypothesis that requires confirmation by proof-of-concept studies. It is far too early to draw conclusions about the efficacy of PRP as a treatment for hip osteoarthritis. The only randomized trial versus hyaluronic acid showed no significant difference in effects, and no placebo-controlled trials are available. Most of the randomized trials in knee osteoarthritis support a slightly greater effect in alleviating the symptoms compared to visco-supplementation, most notably at the early stages of the disease, although only medium-term data are available. Many uncertainties remain, however, regarding the best administration regimen. Serious adverse effects, including infections and allergies, seem rare, although post-injection pain is more common than with other intra-articular treatments for osteoarthritis.