Staphylococcus aureus is the leading cause of human skin infections. In this issue of Cell Host & Microbe, new research probes how a change in surface hydrophobicity mediated by a single S. aureus protein renders the pathogen resistant to key molecular effectors of skin innate immunity, including cationic antimicrobial peptides and fatty acid constituents of sebum. Novel treatment strategies for S. aureus infection may lie in supplementing the very same innate defense molecules to therapeutic levels.