Summary Insects such as Drosophila rely entirely on innate immune responses to combat microbial pathogens. In particular, infection leads to the rapid and massive activation of anti-microbial peptide gene transcription. Drosophila utilize two NF-kappaB signalling pathways to control anti-microbial peptide gene expression, the IMD and Toll pathways. This review highlights recent advances in understanding the mechanisms of bacterial recognition utilized by both these pathways, and in deciphering the mechanisms of intracellular signalling in the IMD pathway. In particular, the peptidoglycan recognition proteins play a critical role in recognizing and discriminating different types of bacterial pathogens, and then activating either the Toll or IMD pathway. Throughout the article, the similarities and differences between Drosophila and mammalian innate immune pathways are discussed.