Staphylococcus aureus is responsible for two main clinical presentations in humans: suppurative infections and toxigenic diseases. A small percentage of S. aureus strains secrete Panton-Valentine leukocidin (PVL). This toxin is implicated in skin infections, furunculosis, osteoarticular infections, and particularly, in serious pulmonary infections known as necrotizing pneumonia, which affect immunocompetent patients with no comorbidity. A clear outline of the clinical presentation was described recently. Necrotizing pneumonia caused by PVL-secreting S. aureus strains is characterized by a combination of fever, hemoptysis, multilobar alveolar infiltrations, and leukopenia. The disease usually progresses to toxic shock or refractory hypoxemia. A number of interesting therapies targeting leukocidin have been proposed over the past few years based on in vitro data. This review focuses on the physiopathological basis and on the therapeutic relevance of various drugs.