The Toll-like receptors (TLRs) are key molecules involved in the recognition of pathogens by the innate immune system. This family of germ line-encoded receptors has evolved to recognize conserved features of microbes. Currently, 10 TLR family members have been identified in mammals. The number of ligands for these receptors continues to grow, and it seems clear that multiple ligands exist for each receptor. Whether engagement of different TLRs leads to differences in gene expression and thereby differences in the immune response remains to be seen. However, recent work has demonstrated that activation of TLRs is required for initiation of only certain adaptive immune responses.