Toll-like receptors (TLRs) are highly conserved throughout evolution. They play an essential role in initiating the innate immune response against infectious pathogens. In Drosophila, toll is required for anti-fungal response, while the related 18-wheeler is involved in antibacterial defence. In humans, ten members of the TLR family protein (TLR1 to TLR10) have been identified. TLRs recognize a wide variety of pathogen-associated molecular patterns from bacteria, viruses, and fungi and elicit a wide array of antimicrobial responses. Among TLRs, TLR6 is expressed on the cell surface of monocytes, monocyte-derived immature dendritic cells (iDCs), and neutrophils, but not on B, T or natural killer (NK) cells. Human TLR6 is a 796-aa type l transmembrane protein that is 74% identical with mouse. It contains an N-terminal signal peptide, 19 tandemly repeated extracellular leucine-rich motifs, and a cytoplasmic domain called Toll/IL-1R homology domain, as seen in other TLRs. TLR6 function has been studied mainly in mouse cells. Constitutive expression of TLR6 activates both the nuclear factor kappa-B (NFK-B) and Jun N-terminal kinase (JNK) pathways. Studies in human cells revealed that TLR6 and TLR2 colocalize at the plasma membrane of monocytes. Human TLR6 recognizes diacylated lipoprotein and peptidoglycan at the cell surface cooperatively with human TLR2. Thus, coexpression of TLR2 and TLR6 at the cell surface is crucial for recognition of diacylated lipopeptide and peptideoglycan and subsequent cellular activation in human cells.