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Drosophila melanogaster is an established model organism for the study of host–pathogen interactions. The sequencing of its genome allowed the prediction of all the genes encoded in it and, consequently, enabled a more comprehensive view of its immune responses. Whole-genome transcription analyses of Drosophila response to bacteria, fungi, parasitoids and viruses allow a comparison of the response between different classes of microorganisms and between pathogens of the same class. Overall, there is great diversity in the immune responses but there are a few pathways that are frequently activated. These studies provide a better understanding of how the host resists the infection and responds to the associated damage. Moreover, the data give insights into how microorganisms can manipulate their host and successfully establish an infection.