Sepsis is a major cause of death worldwide. In recent years it has become clear that most septic patients do not die from an overwhelming initial pro-inflammatory immune response, but die in the subsequent immunosuppressive phase, called 'immunoparalysis', which is characterized by increased susceptibility to secondary and opportunistic infections. Although infection control and supportive therapies, especially in the early phase of sepsis, will remain the cornerstone of treatment, the discovery of immunoparalysis and its detrimental effects currently causes a profound shift in the sepsis research field. Hitherto, whereas research into sepsis therapies predominantly focused on suppression of the immune system (for example with anti-cytokine therapies or glucocorticoids), recent studies increasingly concentrate on immunostimulatory treatment. Promising immunostimulatory compounds such as interferon-γ (IFN-γ) and granulocyte-macrophage colony stimulating factor (GM-CSF) have already shown promising results in experimental settings, and are currently studied in clinical trials.