Stem cells exist in many niches throughout the body and have the ability to self replicate and to differentiate to many lineages. As of a result of the advances in stem cell-based therapies, regenerative medicine is witnessing remarkable development. Encouraging positive outcomes from the use of stem cells in various diseases are extremely promising.. The popularity of stem cell-based therapy is due to its flexibility and potent approach in the treatment of numerous diseases. Treatment with genetically configured HSCs favors the engraftment of transplantation without rejection. MSCs hold an immunoregulatory capacity, elicit immunosuppressive effects and are immune-privileged cells, due to the low expression of MHCII and costimulatory molecules on their cell surface. Encouraging, positive outcomes from the use of stem cells in immunodeficiency, cancer, hemoglobinopathy, bone, cartilage repair, autoimmune disorders, cardiac and neuronal diseases are extremely promising. Successful stem cells based clinical trials are the game changers in the progress of clinical use of stem cells. This review provides an up to date comprehensive overview of the clinical efficacy of stem cells.