The ability of a host to sense invasion by pathogenic organisms and to respond appropriately to control infection is paramount to survival. In the case of sepsis and septic shock, however, an exaggerated systemic response may, in fact, contribute to the morbidity and mortality associated with overwhelming infections. The innate immune system has evolved as the first line of defense against invading microorganisms. The Toll-like receptors (TLRs) are a part of this innate immune defense, recognizing conserved patterns on microorganisms. These TLRs and their signaling pathways are represented in such diverse creatures as mammals, fruit flies, and plants. Ten members of the TLR family have been identified in humans, and several of them appear to recognize specific microbial products, including lipopolysaccharide, bacterial lipoproteins, peptidoglycan, and bacterial DNA. Signals initiated by the interaction of TLRs with specific microbial patterns direct the subsequent inflammatory response. Thus, TLR signaling represents a key component of the innate immune response to microbial infection.