Excessive and unregulated inflammation contributes to multiorgan failure and death in sepsis. Triggering receptor expressed on myeloid cells type 1(TREM-1) is expressed on neutrophils and monocytes and is upregulated in the presence of bacterial pathogens. Engagement of TREM-1 results in increased expression of proinflammatory chemokines and cytokines and amplifies the inflammatory response. In this article, we will review the structure and signaling pathway of TREM-1 and review the role of TREM-1 and soluble TREM-1 in the inflammatory response during sepsis. Based on these studies, modulation of the TREM-1 signaling pathway has been suggested as a potential therapeutic strategy for the treatment of sepsis, to dampen the inflammatory response without interrupting the ability of the host to clear pathogens. This basic science research may someday lead to other treatments for sepsis and other diseases.