Osteoarthritis is a chronic degenerative joint disorder characterized by articular cartilage destruction and osteophyte formation. Chondrocytes in the matrix have a relatively slow turnover rate, and the tissue itself lacks a blood supply to support repair and remodeling. Researchers have evaluated the effectiveness of stem cell therapy and tissue engineering for treating osteoarthritis. All sources of stem cells, including embryonic, induced pluripotent, fetal, and adult stem cells, have potential use in stem cell therapy, which provides a permanent biological solution. Mesenchymal stem cells (MSCs) isolated from bone marrow, adipose tissue, and umbilical cord show considerable promise for use in cartilage repair. MSCs can be sourced from any or all joint tissues and can modulate the immune response. Additionally, MSCs can directly differentiate into chondrocytes under appropriate signal transduction. They also have immunosuppressive and anti-inflammatory paracrine effects. This article reviews the current clinical applications of MSCs and future directions of research in osteoarthritis.