Suicide gene therapy is based on transfer of a suicide viral or a bacterial gene into tumor cells. Expression of these genes leads to non-toxic substances in cell convert to lethal chemotherapeutic agents. However this approach to gene therapy has been widely welcomed by gene researchers and successfully used in many in-vivo and in-vitro researches, but in the case of human clinical trials, the results were not repeated and hadn’t appropriate clinical consequence. Nevertheless, current studies on preclinical models of cancer revealed that suicide gene therapy has the high potential when have been used in combination with novel therapeutic strategies. This review article summarized the various types of suicide gene strategies as well particular highlighting the recently developed suicide gene therapy in humans and their adverse effects. Moreover, the diverse systems which have been used along with suicide gene therapy were reviewed. Finally, this article provides some perspectives into the future of this approach, particularly for eradication of tumor stem cells.