The Toll signaling pathway, which is required for the establishment of the dorsal–ventral axis in Drosophila embryos, plays an important role in the response of larval and adult Drosophila to microbial infections. Recent genetic evidence has shown that a mammalian Toll-like receptor, mouse Tlr4, is the signal transducing receptor activated by bacterial lipopolysaccharide. Thus, Toll-like receptors appear to detect a variety of microbial components and to trigger a defensive reaction in both Drosophila and mammals. Genetic data from both Drosophila and mice have defined components required for activation of Toll-like receptors and for the downstream pathways activated by the Toll-like receptors.