Septic shock is one of the leading causes of death in intensive care units world-wide. Scientists have made great improvements in understanding mechanisms of inflammation, and the sequence of activation of the various pro- and anti-inflammatory markers is now well known. In contrast, physicians have failed to improve survival from septic shock despite the development of specific targets at various points in the cytokine cascade considered to have a key role in host survival in sepsis. Corticosteroids were among the first anti-inflammatory drugs to be tested in large randomized controlled trials. These trials showed that patients with septic shock did not benefit from a short course of large doses of steroids. More recent findings highlighting the role of the integrity of the hypothalamic—pituitary—adrenal axis to respond appropriately to a septic insult, have led to a re-appraisal of the use of steroids in septic shock. Several randomized controlled trials have evaluated the efficacy of a replacement therapy with hydrocortisone in severe sepsis. These trials strongly suggest that this replacement therapy reduces the morbidity of septic shock and may favorably affect survival from septic shock.
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