Chagas disease results from infection with the parasiteTrypanosoma cruzi. This disease remains a significant cause of morbidity and mortality in central and south America. Chagas disease now exists and is detected worldwide because of human migration. Control of Chagas disease has relied mainly on vector eradication however, the development of insect resistance to pesticides, coupled with cost and adverse health effects of insecticide treatments, has prompted our group to investigate novel methods of transmission control. Our laboratory has been instrumental in the development of the paratransgenic strategy to control vectorial transmission ofT. cruzi. In this paper, we discuss various components of the paratransgenic approach. Specifically, we describe classes of molecules that can serve as effectors, including antimicrobial peptides, endoglucanases, and highly specific single chain antibodies that target surface glycoprotein tags on the surface ofT. cruzi. Furthermore, we address evolving concepts related to field dispersal of engineered bacteria as part of the paratransgenic control strategy and attendant risk assessment evaluation.