Even at the turn of the millennium, respiratory infections exact a heavy toll on the American public. Pneumonia is the leading infectious disease cause of death, and influenza costs Medicare more than $1 billion each year. This article highlights some of the advances this past year in antimicrobial therapy for respiratory tract infections. Efforts are targeted at shortening the length of treatment and reducing costs for pneumonia. A promising new class of antivirals has been introduced for the treatment of influenza, and alternative medicine continues to receive more scientific scrutiny. Antimicrobials alone are not the answer, and preliminary work on immunomodulatory therapies may usher in a new era of multifaceted treatment approaches.