Premature ovarian failure (POF) is a devastating condition for women of childbearing age with serious health consequences including distress, infertility, osteoporosis, autoimmune disorders, ischemic heart disease, and increased mortality. In addition to the mainstay estrogen therapy, stem cell therapy has been tested as the result of rapid progress in stem cell biology and cell reprogramming. We hereby provide a review for recent research and issues related with stem-cell-based therapy for POF, and provide a commentary on various methods for enhancing the effect of stem cell therapy for POF. Large amount of animal studies have demonstrated an extensive benefit of stem cells for failed ovarian recovering. As shown by such studies, stem cell therapy can result in recovery of hormone levels, follicle activation, ovarian angiogenesis and function restoration. Meanwhile, study of molecular pathways revealed that the function of stem cells mainly depends on their paracrine actions, which may produce multiple factors for the promotion of ovarian angiogenesis and regulation of cellular functions. Nevertheless, study of the disease model also revealed certain drawbacks. Clinical trials have shown that menstrual cycle and even pregnancy may occur following transplantation of stem cells in POF cases, albeit the limitations including inadequate number of cases and space for the improvement of transplantation methodology. Only with the improvement of safety and function assessment and expansion of clinical trials, can stem cell therapy bring benefits to more women with POF. Additionally, effective pre-treatments and appropriate transplantation methods for stem cells are also required. Taken together, stem cell therapy has shown a great potential for POF recovery and is promising to step from bench to bedside.