The innate immune system is an evolutionally conserved host defense mechanism against pathogens. Innate immune responses are initiated by pattern recognition receptors (PRRs), which recognize microbial components that are essential for the survival of the microorganism. PRRs are germline-encoded, nonclonal, and expressed constitutively in the host. Different PRRs react with specific ligands and lead to distinct antipathogen responses. Among them, Toll-like receptors (TLRs) are capable of sensing organisms ranging from bacteria to fungi, protozoa, and viruses, and they play a major role in innate immunity. Here, we review the mechanism of pathogen recognition by TLRs.