Osteoarthritis (OA) is a chronic joint disease that generally occurs worldwide with pain and disability. The progression is slow, and it is mostly diagnosed midlife and often disturbs the knees, hips, feet, hands, and spine. Sex, age, obesity, occupation, and hereditary factors are risk factors that increase the opportunity for OA. Physical examinations involving X-rays and MRI, joint fluid analysis and blood tests are common tools for the diagnosis of OA. Interventions including exercise, manual therapy, lifestyle modification, and medication can help relieve pain and maintain mobility in the affected joints, yet none of the therapies enables the promotion of regeneration of degenerated tissues. Mesenchymal stem cells (MSCs) are a promising source for the treatment of OA due to their multipotency for differentiation into chondrocytes and their ability to modulate the immune system. Herein, we review the pathogenesis and treatment of OA and address the current status of MSCs as a novel potential therapeutic agent in OA treatment.