This review summarizes new insights in the pathophysiologic implications of inflammation and microvascular alterations in organ dysfunction, as well as genetic factor contribution, from clinical and experimental studies that were published in 2010 in Critical Care in the fields of multiple organ dysfunction and sepsis. New diagnostic and prognostic markers of organ dysfunction are presented. Evaluations of novel therapeutic strategies, including implementation of international guidelines, modulation of inflammation and coagulation, and prevention of ventilator-induced lung injury and acute kidney injury, are reported. The results of these experimental studies and clinical trials are discussed in the context of the current relevant scientific and clinical background.