Providing antibiotics is a life-saving intervention in patients with septic shock. Cultures as clinically appropriate before antimicrobial therapy are required. Guidelines recommend providing broad-spectrum antibiotics within the first hour after recognition of shock. The site of infection, the patient's history and clinical status, and the local ecology all affect the choice of empirical treatment. The appropriateness of this choice is an important determinant of patient outcome. At 48-96h, the antimicrobial treatment should be systematically reassessed based on the clinical course and culture results. Cessation, de-escalation, continuation, or escalation are discussed according to these variables. Unnecessary treatment should be avoided to reduce the emergence of multidrug resistant pathogens.