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The past several years have seen remarkable advances in understanding the basic cellular and physiologic mechanisms underlying organ dysfunction and recovery relating to sepsis. Although several new therapeutic approaches have improved outcome in septic patients, the far-reaching potential of these new insights into sepsis-associated mechanisms is only beginning to be realized.The Brussels Round Table Conference in 2006 convened >30 experts in the field of inflammation and sepsis to review recent advances involving sepsis and to discuss directions that the field is likely to take in the near future.Current understanding of the pathophysiology underlying sepsis-induced multiple organ dysfunction highlights the multiple cell populations and cell-signaling pathways involved in this complex condition. There is an increasing appreciation of interactions existing between different cells and organs affected by the septic process. The intricate cross-talk provided by temporal changes in mediators, hormones, metabolites, neural signaling, alterations in oxygen delivery and utilization, and by modifications in cell phenotypes underlines the adaptive and even coordinated processes beyond the dysregulated chaos in which sepsis was once perceived. Many pathologic processes previously considered to be detrimental are now viewed as potentially protective. Applying systems approaches to these complex processes will permit better appreciation of the effectiveness or harm of treatments, both present and future, and also will allow development not only of better directed, but also of more appropriately timed, strategies to improve outcomes from this still highly lethal condition.