Toll-like receptors (TLRs) play a critical role in the detection of invading pathogens and subsequent immune response against them. Individual TLRs recognize distinct microbial components. The TLR is a type 1 transmembrane receptor that is composed of an extracellular leucine-rich repeat (LRR) domain and cytoplasmic domain homologous to that of the IL-1R family. Therefore, TLR and IL-1R family use the same signaling molecules. Cytokine production in response to each TLR ligand is completely abolished in MyD88-deficient cells, indicating that MyD88 is an essential signaling molecule shared among IL-1R/Toll family. However, accumulating evidence indicates that differential utilization of adaptors including MyD88, TIRAP, and TRIF may activate overlapping as well as distinct signaling pathways, and finally give rise to distinct biological effects exerted by individual TLR family.