Despite advances in antimicrobial therapy and supportive measures, mortality in patients with severe community- acquired pneumonia admitted to the intensive care unit remains high, especially in case of development of sepsis with its complications. Systemic inflammation is a major feature of severe community-acquired pneumonia worsening to sepsis. This uncontrolled inflammation is sustained by genetic mechanisms throughout an exaggerated activation of the nuclear factor NF-B. Glucocorticoids inhibit the activity of NF-κB intracellularly. On the base of this concept, the data emerged from scientific literature and from a recent randomized trial on patients with severe community acquired pneumonia support the hypothesis that prolonged infusion of low doses of hydrocortisone may accelerate the resolution of the pneumonia and prevent the development of severe complications due to sepsis. Moreover, this therapeutic approach seems to be associated with a significant reduction in duration of mechanical ventilation, length of hospital stay and long-term mortality.