Toll-like receptors (TLRs) have a unique and important role in detecting the presence of pathogenic infection. TLRs can recognize conserved structures from a wide variety of microorganisms, such as bacteria, mycobacteria, spirochetes and yeast. However, they are generally not thought to play a major role in viral infection. Several reports have now identified distinct viral ligands for the TLRs, and evidence is accumulating for a functional role of the TLRs in mediating antiviral effector mechanisms.