 Alpha hemolysin is a poor-forming toxin produced by Staphylococcus aureus that causes tissue barrier disruption and injury, and has been recognized as an important cause of disease in skin necrosis and lethal infection. Recent studies have identified Adam 10 as a cellular receptor for alpha hemolysin, providing insight into the molecular mechanisms by which the toxin causes tissue damage during disease pathogenesis. This review highlights historical studies on alpha hemolysin and key findings on its structural and functional biology, as well as emerging observations that have expanded our understanding of this toxin in aureus disease. This article was authored by Brian J. Barubi and Julianne Bubeck-Wartenburg.