Infections are among the most common diagnoses in the emergency department (ED), and antibiotics are among the most frequently prescribed drugs. Community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) are frequently encountered in the ED, and pneumonia is the seventh leading cause of death in the United States. Cystitis, pyelonephritis, and complicated urinary tract infection (UTI) are often treated in the ED, with UTI being one of the most common reasons for healthy young women to require antimicrobial treatment. Intra-abdominal infections have an incidence of 3.5 million cases per year in the United States, and emergency clinicians must make complex decisions regarding appropriate evaluation and management. Skin and soft-tissue infections (SSTIs) are common, their incidence in the ED has been rising, and the emergence of methicillin-resistant Staphylococcus aureus (MRSA) infection has altered their management. Timely diagnosis and management of infectious disease, including proper antimicrobial treatment, is an important goal of emergency care. This issue of Emergency Medicine Practice reviews the available evidence and consensus guidelines for the management of common infectious diseases presenting to the ED and presents recommendations for treatment.