Surprisingly, it remains unclear whether the single most effective development in humanity’s fight against bacterial infection—the antibiotic—has helped to decrease either the morbidity or mortality of thoracic empyema.4,5 In the nearly 70 years since antibiotics became widely available, no serious, large-scale trials have been conducted to explore their optimal combination, delivery method, or duration of administration. Thoracic empyema remains a primarily surgical disease; antibiotics penetrate empyemata poorly, allowing for the largely undisturbed accumulation and organization of damaging fibropurulence. Guidelines for treatment focus heavily on invasive maneuvers such as drainage and fibrinolysis, mentioning antibiotics only as adjuvant therapy. What is universally agreed upon is that antibiotic recommendations are not evidence-based. Instead, research efforts have understandably focused on optimizing invasive methods of reducing and removing purulence and scarring. In recent years, studies have established the merits of video-assisted thorascopic surgery with pleural debridement as opposed to open thoracotomy,6 the superiority of small- over large-bore chest tubes,7 and the role of imaging guidance in drainage.8 Although we have learned a few things about the best surgical and fibrinolytic approaches to thoracic empyema, its optimal antibiotic therapy remains opaque.