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.