Intensive care units (ICUs) care for the most severely ill patients and consequently account for the largest volume of antibiotic use in the hospital. Critically ill patients must receive optimal, timely empiric antibiotic therapy. However, there are opportunities to improve overall antibiotic use in the ICU by ensuring that antibiotics are de-escalated based on culture and clinical data or stopped if an alternative, noninfectious diagnosis is determined. Further, shorter durations of therapy based on clinical trials should be selected to minimize antibiotic exposure. ICUs should work with hospital antibiotic stewardship programs to review antibiotic use and determine areas for improvement.