Antimicrobial peptides are pivotal elements of the innate immune defense against bacterial and fungal infections. Within the impressive list of antimicrobial peptides available at present, more than half have been characterized in arthropods. Cysteine-rich antimicrobial peptides represent the most diverse and widely distributed family among arthropods and, to a larger extent, among invertebrates. Proeminent groups of cysteine-rich peptides are peptides with the CS alpha beta motif and peptides forming an hairpin-like beta-sheet structure. Although these substances exhibit a large structural diversity and a wide spectrum of activity, they have in common the ability to permeabilize microbial cytoplasmic membranes. Drosophila has proved a remarkable system for the analysis of the regulation of expression of gene encoding antimicrobial cysteine-rich peptides. These studies have unraveled the striking parallels that exist between insect immunity and innate immunity in mammals that point to a common ancestry of essential aspects of innate immunity.