Purpose of review To provide a current overview of sepsis pathophysiology. Recent findings The emphasis on sepsis pathophysiology has moved away from the pathogen - the initiating factor - and instead is focussed upon the abnormal and exaggerated host response. Instead of targeted eradication of the infection, the host response activates or suppresses multiple downstream pathways, leading to multiple organ dysfunction. Summary Sepsis represents a dysregulated host response to infection leading to organ dysfunction. Here, the pathogen triggers an initial exaggerated inflammatory-immune response that leads to activation or suppression of multiple endothelial, hormonal, bioenergetic, metabolic, immune, and other pathways. These, in turn, produce the circulatory and metabolic perturbations resulting in organ dysfunction. This review will provide an overview of underlying mechanisms and propose that these processes, whereas superficially viewed as dysfunctional, may actually be adaptive/protective in the first instance, though spilling over into maladaptation/harm depending on the magnitude of the host response.

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