In 1997, a human homologue of the Drosophila Toll protein was described, a protein later to be designated Toll-like receptor 4 (TLR4). Since that time, additional human and murine TLR proteins have been identified. Mammalian TLR proteins appear to represent a conserved family of innate immune recognition receptors. These receptors are coupled to a signaling pathway that is conserved in mammals, insects, and plants, resulting in the activation of genes that mediate innate immune defenses. Numerous studies have now identified a wide variety of chemically-diverse bacterial products that serve as putative ligands for TLR proteins. More recent studies have identified the first endogenous protein ligands for TLR proteins. TLR signaling represents a key feature of innate immune response to pathogen invasion.