Morbidity and mortality associated with the development of severe sepsis remain unacceptably high. However, with the introduction of a protocol called early goal-directed therapy, significant benefits in terms of patient's outcome have been demonstrated. In an aim to improve outcome and to increase awareness, practical evidence-based guidelines for the management of severe sepsis and septic shock were developed under the auspices of the Sepsis Surviving Campaign, easy to apply by the bedside medical and nursing staff. The treatment of severe sepsis includes 3 main essentials: (1) eradication of the inciting infection using source control measures and empiric antimicrobials, (2) hemodynamic resuscitation of tissue hypoperfusion using fluids and inotropic drugs to prevent life-threatening organ damage, and (3) sustained organ support using mechanical interventions to diminish organ injury. This review article highlights the anti-infective approach of the management of sepsis.