Publisher Summary This chapter describes the basic techniques currently used to both infect Drosophila and to monitor corresponding immune responses. Research on pathogens such as Listeria, Yersinia, Salmonella, Shigella, Escherichia, which are particularly suitable to genetic manipulation, have increased understanding of the molecular interactions between bacterial factors and host cellular components. Two methods are used for infecting Drosophila: (1) Microbial injection-a direct introduction of bacteria and fungi into the body cavity of the fly, and (2) Natural infection without injury. Most of the techniques described here are simple and do not require extensive skills or complex devices. Therefore, it requires very little to test the effect of each experimenter's favorite pathogen on Drosophila; if the pathogen shows an effect, powerful genetic and molecular tools can be applied to identify host factors that are the target of these microorganisms. In this context, one should keep in mind that some of the medically important bacteria are also pathogenic for fly. In this case, Drosophila also provides an easy assay to screen mutated microbes for the loss of virulence factors.