The emergency department (ED) is the hub of the US health care system. Acute infectious diseases are frequently encountered in the ED setting, making this a critical setting for antimicrobial stewardship efforts. Systems level and behavioral stewardship interventions have demonstrated success in the ED setting but successful implementation depends on institutional support and the presence of a physician champion. Antimicrobial stewardship efforts in the ED should target high-impact areas: antibiotic prescribing for nonindicated respiratory tract conditions, such as bronchitis and sinusitis; overtreatment of asymptomatic bacteriuria; and using two antibiotics (double coverage) for uncomplicated cases of cellulitis or abscess.