Treatment of soft and hard connective tissues especially those associated with massive tissue loss is technically demanding. Tendon and cartilage have low healing capability. Massive bone injures are often associated with nonunion or malunion and other complications. Treatment of tendon-bone junction is challenging and treatment of osteoarthritis is more palliative than curative. Tissue engineering which composed of three elements including scaffolds, healing promotive factors such as growth factors, and stem cells is an option. Recently stem cell based therapy is much popular due to the encouraging reported results. This review introduced stem cells and discussed their potential application and roles in tissue regenerative medicine. We have focused on the effectiveness of stem cells based therapy on different tissue injuries, including tendon, tendon to bone junction, bone, cartilage and osteoarthritis. In vitro to clinical evidences have been discussed in detail with the aiming to conclude whether stem cell based therapy is a clinically accepted method. This review showed that despite of exploring several sources for the stem cells, the adult mesenchymal stem cells are still the only reliable stem cells in tissue regenerative medicine.In addition, despite of significant improvement in tissue engineering, it seems cell seeding is technically demanding and direct injection of the stem cells is the only reliable method for cell delivery at injured site. Because of controversial results and lack of well-designed clinical trial studies, this review also showed that despite of several animal studies and application of stem cells on various tissue injuries, it is still soon to suggest stem cell therapy as an effective method in restoring morphology and functionality of the injured tissues.