Much research has gone into the molecular aspects of trypanosome biology in the mammalian host. Significantly less is known about the parasite developmental processes in the tsetse fly. This knowledge can be important for the development of tsetse-based methods to interfere in parasite transmission to reduce disease. Our studies on vector-trypanosome biology focus on two areas. First, we aim to understand the differentiation, establishment, and maturation processes of the parasite in the fly. Secondly, this information is used to examine how the fly interacts with, and responds to the parasite at each of these developmental stages. Related to this, we investigate the molecular aspects of tsetse immunity during parasite transmission with the eventual goal of manipulating these responses to block disease transmission. These data will pave the way to novel disease and vector control strategies.