Toll-like receptors (TLRs) play an essential role in the detection and elimination of invading microbes. They are type-1 transmembrane receptors, containing extracellular leucine rich repeats and an intracellular Toll/interleukin-1 receptor (TIR) domain. Upon stimulation, these receptors interact with specific TIR domain-containing adaptor proteins. Five such adaptors have been discovered to date, MyD88, Mal (MyD88 adaptor-like)/TIRAP (TIR domain-containing adaptor protein), Trif (TIR-domain-containing adaptor inducing interferon-beta), TRAM (Trif-related adaptor molecule) and SARM (SAM and ARM-containing protein). Different TLRs use different combinations of these adaptors, leading to the activation of common and unique pathways involved in the elimination of the invading microbe.