An important goal of this review has been to convince readers from other fields that flies provide a broad range of advantages for studying host-pathogen interactions at the level of the cell, tissue, organ and intact organism. As discussed, genome-wide RNAi screens in Drosophila cell culture have generated a wealth of new information regarding the genes involved in mediating basic host cellular responses to pathogens, such as those involved in innate immunity, phagocytosis and restriction of intracellular pathogen survival. These cellular studies can be complemented by studies that aim to identify host resistance factors and pathogen virulence factors using intact flies as infection models. Studies in flies also provide the potential to explore mutualistic interactions with intracellular endosymbionts, and to conduct mechanistic analysis of specific virulence factors, and combinations of these factors, using the state-of-the-art genetic tools available in Drosophila.