Drosophila melanogaster is a powerful model to study infections thanks to the power of its genetics and knowledge on its biology accumulated for over a century. While the systemic humoral immune response against invading microbes has been intensively studied in the past two decades, the study of intestinal infections is more recent. Here, we present the methods that are currently in use to probe various aspects of the host-pathogen interactions between Drosophila and ingested microbes, with an emphasis on the study of the midgut epithelium, which constitutes the major interface between the organism and the microbe-rich ingested food.