The triggering receptor expressed on myeloid cells (TREM)-1 is a recently identified molecule that is involved in monocytic activation and the inflammatory response. It belongs to a family related to natural killer cell receptors, and is expressed on neutrophils, mature monocytes and macrophages. The engagement of TREM-1 synergizes with the activation of several toll-like receptors in amplifying the inflammatory response mediated by microbial components. The modulation of the TREM-1 signaling pathway, by the use of small synthetic peptides derived from its extracellular domain, confers interesting survival advantages during experimental murine septic shock, even when administered late after the onset of sepsis.