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Sepsis is a common condition with high morbidity and mortality. Although many patients may require critical care, this article considers the features of sepsis that are of most relevance to acute general physicians. Recently updated definitions of sepsis and septic shock have been proposed which better identify patients who are likely to have a poor outcome, and therefore give an opportunity to escalate care. Despite these advances, there is still no molecular signature able to diagnose sepsis. Pathogenesis is complex, with many immune and non-immune mediators involved. Four key areas are endothelial dysfunction, coagulation abnormalities, alterations in cell function and dysregulated cardiovascular responses. No specific therapy targeting the mediators of sepsis has yet proven effective. Prompt administration of appropriate antibiotics is of benefit, together with fluid resuscitation and oxygen.