The insulin/insulin growth factor 1 signaling (IIS) cascade regulates a wide range of mosquito physiologies in a tissue dependent manner. A key IIS regulated tissue in mosquitoes is the fat body, where work in our labs and others have shown the impact of IIS on metabolism, lifespan, innate immunity and other important physiological processes that directly affect vectorial capacity. We will examine fat body IIS in mosquitoes and other dipterans to explore how these broad physiologies are regulated by this important signaling cascade. We will also explore how fat body IIS and insulin-like peptides expressed in the fat body coordinate an organism wide response to nutrient uptake and pathogen challenges. Finally, we will look into unanswered questions regarding fat body IIS and how it manipulates mosquito biology as well as future directions that still need to be explored.