Mammals defend themselves against microorganisms via two defense mechanisms: the adaptive, antibody-based immune response and the innate response, which is a very important first line defense. This innate immune system exists in all animals whereas the antibody-derived system occurred only once during evolution, in the first vertebrates. Insights into the antimicrobial defense of the fruit fly Drosophila melanogaster have shown striking parallels between insect and mammalian innate immunity. In insects, an infection provokes the rapid synthesis of powerful antimicrobial peptides by the fat body (an equivalent of the liver). The pathways, which control the expression of those peptides, are now understood. Understanding this process in flies has given invaluable insights into the human immune response. The identification of the genes involved in the control of innate immunity will reveal new targets for therapeutic agents that become necessary, in view of the growing importance of nosocomial infections or opportunistic fungal infections in immunodepressed.