It has become clear that Staphylococcus aureus is a facultative intracellular microorganism. Adherence and invasion are a prerequisite for endovascular infections caused by S. aureus, such as infective endocarditis. These phenomena may also be involved in the pathogenesis of invasive and metastatic infection upon hematogenous dissemination, such as osteomyelitis and abscess formation. The underlying molecular mechanism has been elucidated in detail, including its likely relevance in vivo. However, the mode of action of recently identified modulators of invasion, such as pls/Pls have not yet been clarified. The potential outcome for host cells and S. aureus following invasion are diverse. Surprisingly, induction of apoptosis in human endothelial cells is more complex than previously thought, since it appears to involve multiple virulence factors. In the light of increasing resistance to antimicrobial therapy, understanding the multifacetted pathogenesis of S. aureus infection in detail is needed for a better prevention and therapy.