In this issue of Virulence, Rouha et al have thoroughly evaluated the capacity of a pair of human monoclonal antibodies to inhibit the cytotoxicity of the leukocidins and Hla . These antibodies, termed ASN-1 and ASN-2, were isolated by screening a human IgG1 antibody library using a yeast selection system; ASN-1 exhibits cross-reactive neutralizing activity against Hla and four of the leukocidins (PVL, LukED, and the γ-hemolysins), while ASN-2 neutralizes LukAB/LukGH. The authors have previously reported the cross-reactive capacity of ASN-1 , itself an important discovery given the redundant nature of S. aureus virulence factor expression. In this report, Rouha and colleagues characterize the individual and combined effects of the mAbs in a variety of in vitro models using human leukocytes, an important distinction given leukocidin tropism.