Ischemic stroke is one of the leading causes of death and disability worldwide. There is no effective treatment for ischemic stroke apart from thrombolytic therapy, which has a narrow therapeutic time window. Gene therapy has proven to be effective in experimental stroke, but it suffers from disadvantages that limit its clinical application, such as difficulty in intracranial delivering of therapeutic genes, low efficacy in transfecting host cells and long-term expression of exogenous genes. Delivering therapeutic genes to the ischemic brain via stem cells is an alternative strategy of combined gene and stem cell therapy. There are advantages for stem cell-mediated gene delivery as opposed to direct gene transfer. In recent years, studies used stem cells that over-express different neurotrophic factors, such as BDNF, GDNT, or NT3, and found that the delivery of these genetically-modified stem cells to animal models of ischemic stroke is safe and effective, thus suggesting that stem cell-based gene therapy may be a promising treatment for stroke. This review summarizes the advantages and recent progress of stem cell-based gene therapy for ischemic stroke. We also discuss the relevant strategy for optimizing stem cell-based gene therapy and discuss the potential strategies for its future application.