Osteoarthritis (OA) is a degenerative joint disease that, despite recent progress, has no curative treatment. Considerable research has recently been initiated to identify new potential therapeutic targets. In this review, we will set forth some of the major discoveries in the past 5 years, notably those dealing with the identification of pathogenic factors [hypoxia-inducible factors (HIFs), complement, transforming growth factor (TGF)-β and zinc-ZIP8]. New drugs and concepts currently in clinical development [anti-nerve growth factor (NGF), mesenchymal stromal cells and fibroblast growth factor (FGF)-18] will then be addressed. Finally, we will consider prospective avenues that could lead to mid-to-long-term developments of novel therapeutic concepts, notably those dealing with autophagy regulation and induced pluripotent stem cells.