Attenuated strains of Salmonella typhimurium specifically colonize and proliferate in cancer tissues, resulting in marked tumor reduction or even complete eradication. This chapter focuses on S. typhimurium defective in ppGpp synthesis (ΔppGpp). It describes an approach to cancer therapy using attenuated ΔppGpp S. typhimurium. Delivery and expression of cancer therapeutic genes using engineered attenuated S. typhimurium were found to drastically suppress tumor growth. Following systemic administration to tumor-bearing mice via the tail vein, however, genetically engineered S. typhimurium became initially and transiently localized to reticuloendothelial organs. Attenuated strains of S. typhimurium have shown excellent tumor targeting and induction of robust anticancer activity, and several genetically engineered attenuated strains of S. typhimurium have been tested in tumor models. To increase bacterial anticancer activity, engineered strains of ΔppGpp S. typhimurium have been used as delivery and expression vectors to send payloads specifically to tumor tissues.