Obtaining a precise bacteriological diagnosis before starting antibiotic therapy is, when possible, of paramount importance for the success of therapeutic strategy during sepsis. Two to three blood cultures should be performed, preferably from a peripheral vein, without interval between samples to avoid delaying therapy. A quantitative approach is preferred in most cases when possible, in particular for catheter-related infections and ventilator-associated pneumonia. Diagnosing community-acquired pneumonia is complex, and a diagnostic algorithm is proposed. Appropriate samples are indicated during soft tissue and intraabdominal infections, but cultures obtained through the drains are discouraged.