Introduction Infections are common among intensive care unit (ICU) patients. On any given day, up to 70% of ICU patients receive antimicrobials for treatment of or prophylaxis against infection . Appropriate and timely administration of antimicrobial therapy in the ICU reduces morbidity and mortality in patients with serious infections, particularly when complicated by severe sepsis or septic shock [2,3]. In view of growing antimicrobial resistance worldwide, with fewer and fewer novel agents in development, optimal use of existing antimicrobials is imperative in critically ill patients. Approach to infection in the critically ill patient The decision to initiate antimicrobial therapy should rest upon a reasonable clinical suspicion for infection, buttressed by a thorough diagnostic evaluation. The respiratory tract, abdomen, bloodstream and genitourinary system are the most common sites of infection in patients admitted to the ICU . Soft-tissue infections are also common, but are frequently missed in the early stages. In patients that have undergone invasive procedures or prolonged hospitalization, healthcare-associated infections (e.g. central-line-associated bloodstream infection, ventilator-associated pneumonia, catheter-associated urinary tract infection, surgical-site infection, decubitus ulcers and Clostridium difficile infection) must also be considered. Fever is a common presentation of infection, although it may be blunted or absent in the elderly, the immunocompromised, burn victims and patients receiving renal replacement therapy. It is important to remember that thromboembolic disease (e.g. deep-vein thrombosis, pulmonary embolus), medications, transfusion-related reactions, adrenal insufficiency, certain malignancies and a host of other noninfectious processes may also manifest as fever in the ICU. An initial laboratory investigation should include a complete blood count with differential, metabolic panel, liver function test, coagulation studies and urinalysis. HIV testing is recommended in high-risk populations. Whenever possible, microbiological cultures from probable sites of infection (e.g. blood, urine, sputum, wound) should be obtained before initiating antimicrobials to maximize yield and guide therapy. Depending on clinical suspicion, invasive procedures such as lumbar puncture, thoracentesis or paracentesis should be performed to secure cultures and rule out infection. However, antimicrobial therapy should never be delayed in an unstable patient to obtain cultures. This is particularly true for suspected meningitis, rapidly progressive necrotizing infections and septic shock.