Conserved throughout evolution, mammalian toll-like receptors (TLRs) participate in innate immune response to microbial pathogens. The TLRs mediate activation by microbial ligands, resulting in cytokine activation as well as other host defense mechanisms. Activation of TLRs also can result in tissue injury including manifestations of septic shock and host cell apoptosis. In this manner, the activation of mammalian TLRs in the context of infectious disease can contribute to host defense and immunopathology.