The pathogen Staphylococcus aureus is well adapted to its human host. Neutrophil-mediated killing is a crucial defense system against S. aureus; however, the pathogen has evolved many strategies to resist killing. We first describe the discrete steps of neutrophil activation and migration to the site of infection and the killing of microbes by neutrophils in general. We then highlight the different approaches utilized by S. aureus to resist the different steps of neutrophil attack. Various molecules are discussed in their evolutionary context. Most of the molecules secreted by S. aureus to combat neutrophil attacks at the site of infection show clear human specificity. Many elements of human neutrophil defenses appear redundant, and so the evasion strategies of staphylococci display redundant functions as well. All efforts by S. aureus to resist neutrophil-mediated killing stress the importance of these mechanisms in the pathophysiology of staphylococcal diseases. However, the highly human-specific nature of most host-pathogen interactions hinders the in vivo establishment of their contribution to staphylococcal pathophysiology.