This Reprint focuses on the molecular mechanisms in vitro or in vivo in preclinical models as well as patient studies providing insights into new therapeutic concepts to prevent or treat sepsis progression. Seeing as eradication of the focus and intensive care supply are the only treatment regimens for patients suffering from sepsis, it is obvious that new therapies are mandatory. Because the anamneses of sepsis patients are very heterogeneous, characterizing mechanistic details associated with sepsis initiation or progression will help to establish new therapeutic approaches.