Sepsis is a complex clinical situation responsible for thousands of deaths annually in intensive care units around the globe. Despite all our progress in providing medical care to critically ill patients, mortality of severe forms of sepsis did not decrease as expected. Part of this phenomenon is due to our defective understanding about the host immune response to aggression by a microorganism, including the part played by the pattern-recognition receptors (PRRs) in this process. PRRs are part of the innate immunity responsible for detecting non-self antigens and trigger the initial inflammatory response. The best known PRRs are the tol-like receptors (TLRs). In this article, we review some of our knowledge regarding the role of TLRs in sepsis, both in experimental models and in human patients. The improvement in our knowledge about the mediators and signaling pathways that control this immune response is crucial for the development of better markers of disease and new therapeutic targets, leading us to improve the way we treat septic patients.