Osteoarthritis is the most common chronic degenerative disorder causing painful, deformed, stiff joint leading to progressive deterioration of quality of life. Mesenchymal Stem Cell (MSC) therapy in osteoarthritis has generated great interest and is offered with the unlimited potential of healing and regeneration. Current literature regarding their proper name, optimal sources, mechanisms of action, dosage and route of administration, efficacy, and safety is debatable. This index review article has tried to connect these puzzling pieces of available information and brought clarity on some of these important issues. The author believes that Maintenance Stem Cells (MSC) may be a more suitable term than mesenchymal stem cell or medicinal signaling cells as their origin might not be limited to mesodermal tissue; they have been shown capable of self-renewal, differentiation and maintaining a cascade of healing & possibly regeneration at the implanted site. Only a small percentage of implanted MSC survive and rest undergo apoptosis after releasing growth factors, cytokines, and extracellular vesicles. These surviving MSC become active due to conformational changes induced by anti-environment stimuli and undergo limited self-renewal, proliferation, and differentiation but only a few of them might incorporate into the host tissues, chondrocytes or chondroblast; these cells generate & maintain a momentum of series of regenerative activities to improve the function of joint, stabilize or possibly enhance the cartilage quality. More randomized studies with long term follow-up are required to bring clarity on their ideal source, expansion, culture technique, optimum dosage and route of administration and long-term safety issues.