The Gram-positive bacterium Staphylococcus aureus is a major human pathogen and a common cause of hospital acquired infections. In this IRTG lecture, we will talk about the virulence traits of this versatile pathogen, its virulence factor armamentarium and the regulatory circuits used by the bacterium to fine-tune the expression of these factors. A special focus will be given for adhesion factors and their interaction with host factor components and abiotic surfaces, such as implant medical devices. Additionally, we will talk about the interplay of S. aureus with the host immune system, and about ways to determine S. aureus-host cell interactions in the laboratory.