It is now well established that Toll-like receptors (TLRs) act as primary sensors of microbial compounds. Details of the molecular mechanisms governing TLR responses are emerging steadily and our understanding of the signaling pathways activated these receptors has improved greatly over the last few years. Differences in adaptor usage, cellular localisation and signaling cascades have been elucidated. In this review we will summarize the current understanding of TLR signaling and its regulation.