Host defense against microbes requires the development of an efficient immune response aimed to eradicate the source of infection. Through the expression of a battery of germ-line encoded receptors, including the Toll-like receptors and Nod proteins, the innate immune system, which is a prerequisite to the adaptive immune response, detects microbial motifs and initiates pro-inflammatory signaling. Current research into innate immune function focuses on the nature of the ligands detected by this system, the cell signaling that occurs downstream of receptor activation and finally, how these signals culminate into a tailored adaptive immune response directed to eradicate a specific infection.