Many fascinating questions remain unanswered regarding pore-forming toxin biology and the interaction between these important S. aureus virulence factors and the human host. Despite the robust in vitro characterization of antibody-mediated pore-forming toxin inhibition reported by Rouha and colleagues, gaps remain in our understanding of antibody-toxin interactions in the setting of serious human infections, the setting in which a putative therapeutic would be deployed. For example, our group recently reported that different human antibodies (purified from B-cells obtained from children with invasive S. aureus disease) neutralize LukAB/LukGH-mediated cytotoxicity by distinct mechanisms . It remains unclear whether certain of these mechanisms are more biologically relevant or important in the setting of invasive human infection. Further, evidence of antibody-enhanced disease has been reported in a murine model for at least one of the leukocidins (PVL) , and the relevance of this in humans (both for PVL and the other leukocidins) remains largely unexplored. The authors note that the antibody combination reported in this manuscript is under investigation in a Phase II clinical trial involving mechanically ventilated patients heavily colonized with S. aureus. The findings of this and other future work will hopefully provide further insights into the potential roles of antibody-mediated neutralization of pore-forming toxins in the setting of human disease.