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Osteoarthritis (OA) is a chronic condition affecting millions of people worldwide. Pain and loss of mobility are the main symptoms of OA. Current treatments for OA include non-pharmacological, pharmacological and surgical approaches. Among the pharmacological treatments, intra-articular (IA) therapy is usually offered when systemic oral medication does not provide satisfactory pain relief. The agents most widely used in IA therapy are corticosteroids and hyaluronic acid (HA) preparations. Now, however, multiple novel IA treatments are emerging on the market and their clinical effectiveness is promising. The innovative therapies for OA include new HA preparations such as HYADD® 4 and hybrid association of high and low molecular weight HA (HL-HA). The evidence for the use of platelet-rich plasma (PRP) is increasing, even though unanswered questions remain. Moreover, there are new therapies combining HA with other agents: PRP, polyols (mannitol or sorbitol), chondroitin, or polynucleotides; and all have been trialled with positive results. Novel IA agents proposed for treating OA include clodronate, collagen and mesenchymal stem cell therapy. Finally, further aspects of IA therapy to consider are new drug delivery systems, cost-effectiveness for pain reduction, and appropriate choice of therapy for the phenotype and stage of OA.