Sepsis is a modern medicine icon and the onset of organ dysfunction is one of the worst scenario. More than 100 distinct molecules have been proposed as useful biological markers of sepsis. TNF-alpha, IL-6, chemokines and cytokines are considered the first line factors able to drive the dynamic process of sepsis. The PIRO scheme is a new classification of different aspects, used to stage sepsis. Resuscitation bundles must be started within 6 hours of presentation (serum lactate measured; blood cultures obtained before antibiotic therapy; broad-spectrum antibiotics within 3 hours from emergency admission and 1 hour from ICU admission; in case of hypotension and/or lactate higher than 4 mmol/L deliver an initial 20 ml/kg of crystalloid or colloid solution or apply vasopressors for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure above 65 mmHg). A management bundle should be implemented within 24 hour (low-dose steroids administered for septic shock; recombinant human activated protein C; glucose control maintained at less than 8.3 mmol/L; inspiratory plateau pressures maintained at less than 30 cm H2O).