Mesenchymal stem cells (MSCs) comprise a mixture of various stem cells in myeloid tissue with multipotential differentiation capacity. They can differentiate into bone cells under specific conditions and can be used to treat Osteonecrosis of the femoral head (ONFH) through cell transplantation. This review summarizes research on MSCs in the field of ONFH performed by our team, reveals the progress realized the last 30 years, describes their potential to treat osteonecrosis disease, and analyzes some existing challenges of using MSCs in clinical applications.