Sepsis is the systematic response to infection. In septic patients who develop severe disease, excessive inflammation damages the lungs, liver, kidneys, and cardiovascular system, leading to multiple organ failure and an associated high mortality rate. Sepsis is the leading cause of death in the intensive care unit. The damage to critical organs is primarily due to excessive acute inflammatory response rather than inadequate combat of the infection per se. Impairment of critical organs is closely associated with infiltration of activated neutrophils into those tissues as well as increased activation of endothelial, epithelial, and macrophage populations within the organs to produce a deregulated, overly aggressive inflammatory response. New pharmacological advances hold promise in improving survival from this multi-systemic disorder. Increasing understanding of the signal transduction pathways of inflammatory cells involved in the disease suggests that targeting specific kinases and transcriptional regulatory mechanisms may prove improve outcome from sepsis.