Antimicrobial peptides (AMPs) are ancient defense molecules of the innate immune system. Similarly, neuropeptides are ancient signaling molecules. Similarities in size, cationic charge or amphipatic design between some neuropeptides and AMPs suggest that they might serve an additional function in antimicrobial immunity. This hypothesis, supported by experimental evidence, adds another level of understanding to the intricate crosstalk between the nervous system and the immune system. The recent observation, that another brain protein, amyloid-beta, has antimicrobial activities, suggests that this peptide, prominently known as an accumulating toxic waste material, might have a physiologic function as anti-infective agent.