OBJECTIVE: To review the characteristics of stem cells that may qualify them to be useful as therapeutic agents in sepsis. SUMMARY BACKGROUND DATA: Sepsis is a devastating syndrome and is the leading cause of death among critically ill surgical patients in the United States. Despite decades of research and numerous clinical trials, little progress has been made in the development of new treatments and mortality rates are much the same as they have been for the last 20 to 30 years. As such, sepsis remains a formidable adversary for surgeons and their patients and new therapeutic modalities must continue to be explored. METHODS: Recent literature regarding sepsis and the use of stem cells in the treatment of various inflammatory conditions including sepsis was reviewed. Our experience with the use of stem cells in our own laboratory was included. RESULTS: Stem cells have recently emerged as a promising therapy for a variety of commonly encountered surgical pathologies including cardiovascular disease, neurodegenerative disease, peripheral vascular disease, renal disease, and several others. Their beneficial effects are owed chiefly to their abilities to home to sites of injury and inflammation, to attenuate the inflammatory response, and to accelerate tissue healing and neoangiogenesis in the face of noxious stimuli. CONCLUSIONS: Experimental evidence indicates that stem cells are immunologically responsive cells that home to sites of inflammation and tissue injury. Stem cells also secrete growth factors in response to lipopolysaccharide and tumor necrosis factor that may limit apoptosis and organ injury. Stem cells represent an endogenous therapeutic strategy that may be enhanced for maximum clinical benefit.