Mesenchymal stromal or stem cells (MSCs) are multipotent adult cells that can be isolated from a variety of adult or neonatal tissues, such as bone marrow, fat tissue, placenta or umbilical cord. A therapy based on MSCs can be justified in osteoarthritis (OA) thanks to their differentiation abilities but mostly, to their paracrine and immunosuppressive properties. Possible therapeutic strategies therefore rely on the articular injection of MSCs suspensions for trophic activity or the implantation of MSCs combined with biodegradable materials for tissue engineering applications. Depending on the mode of administration and behavior after implantation, they can decrease local inflammation, prevent chondrocyte hypertrophy and apoptosis as well as differentiate into cartilage-forming chondrocytes. In this review, we summarize pathophysiological and mechanistic data and discuss perspectives confirming the interest of MSCs as a potential therapeutic strategy in OA.