The National Cancer Institute and the American Cancer Society announced that 1.6 million new cancer cases are projected to occur in the USA in 2016. One of the most innovative approaches against cancer is suicide gene therapy, in which suicide-inducing transgenes are introduced into cancer cells. When cancer treatments target the total elimination of tumor cells, there will be no side effects for normal cells. Cancer tissues are targeted through various targeted transport methods, followed by tissue-specific enzymes converting a systemically suitable prodrug into an active drug in the tumor. Suicidal genes are delivered by transporters, such as viral and non-viral vectors, into cancer cells. Suicide gene therapeutic strategies currently pursued are herpes simplex virus thymidine kinase... gene with prodrug ganciclovir, cytosine deaminase gene, carboxyl esterase/irinotecan, varicella zoster virus thymidine kinase/6-methoxypurine arabinonucleoside, nitroreductase Nfsb/5-(aziridin-1-yl)-2,4-dinitrobenzamide, carboxypeptidase G2/4-[(2-chloroethyl)(2- mesyloxyethyl)amino]benzoyl-L-glutamic acid, cytochrome p450-isofosfamide, and cytochrome p450-cyclophosphamide. The goal of this review is to summarize the different suicide gene systems and gene delivery vectors addressed to cancer cells, with a particular emphasis on recently developed systems. Finally, we briefly describe the advantageous clinical applications and potential side effects of suicide gene therapy.