It has been known for quite some time that many pathogenic microorganisms are capable of specifically attenuating or bypassing complement-mediated immune responses. Over the last several years, our understanding of the complement evasion mechanisms utilized by pathogens has increased precipitously through the study of the virulent bacterium Staphylococcus aureus. The combination of structural and functional characterization of S. aureus-derived complement inhibitors has revealed new mechanisms of complement regulation. Study of these proteins may also hold important clues into the design and optimization of long-awaited therapeutics that specifically and effectively block the complement activation and amplification cascades.