Over the past few years, researchers have found that a family of proteins related to the Toll protein of fruit flies, which was first identified as a developmental protein, plays a key role in triggering innate defenses against bacterial and fungal invaders--not only in flies, but in organisms as divergent as tobacco plants and humans. They are finding strong evidence that the innate system not only provides a first line of defense but also alerts the more specialized adaptive immune system to the presence of a dangerous microbe. And there are tantalizing clues that the innate system itself, instead of mounting a single generalized response as long thought, may have specific pathways to target particular pathogens. Drug companies are especially interested in these findings, as they could eventually help scientists design more effective and safer vaccines and provide better treatments for chronic inflammatory and autoimmune diseases and severe microbial infections.