When bacteria invade the human host, they are directly confronted with a serious threat, the human innate immune system. This chapter describes the challenge that a staphylococci face and recent findings on how this bacterium counteracts the massive attack of this innate immune system. In order to survive within the human host, staphylococci have evolved a wide variety of small, excreted proteins that interfere with subsequent steps of the human innate immune system cascade.