For the past two decades therapeutic trials attempting to elicit a change in the host response to infection have failed to improve patients' conditions despite positive preclinical data [87] [88] [89] [90] [91] . However, the results of two recent studies have led to a more promising approach to this problem with recombinant human activated protein C (rhAPC) and low-dose steroids. The hemodynamic effects of steroids have been widely discussed since their use was found to allow early withdrawal of vasopressor treatment in a prospective doubleblinded, multicenter study [92] . The positive effects of steroids on adrenergic receptor cycling and sodium and water balance have been proposed as explanations for this efficacy. Their anti-inflammatory role as well as their anticoagulant effect, caused by limiting membrane expression of tissue factor, may contribute to the clinical benefit. A major difficulty lies in defining adrenal deficiency in septic shock patients, and a number of definitions have thus far been used. A recent retrospective multicenter cohort study conducted by the Corticus study group [93] emphasized the importance of cortisol variation after corticotropin stimulation. That study additionally raised the possibility of a deleterious effect of etomidate on hormonal response and outcome, a concern that was previously reported by others [94] . This specific point is still subject to debate [95] . Efforts are currently being made to define the best strategy for use of steroids during sepsis.