Staphylococcus epidermidis is the most frequently encountered member of the coagulase-negative staphylococci on human epithelial surfaces. It has emerged as an important nosocomial pathogen, especially in infections of indwelling medical devices. The mechanisms that S. epidermidis uses to survive during infection are in general of a passive nature, reflecting their possible origin in the commensal life of this bacterium. Most importantly, S. epidermidis excels in forming biofilms, sticky agglomerations that inhibit major host defense mechanisms. Furthermore, S. epidermidis produces a series of protective surface polymers and exoenzymes. Moreover, S. epidermidis has the capacity to secrete strongly cytolytic members of the phenol-soluble modulin (PSM) family, but PSMs in S. epidermidis overall appear to participate primarily in biofilm development. Finally, there is evidence for a virulence gene reservoir function of S. epidermidis, as it appears to have transferred important immune evasion and antibiotic resistance factors to Staphylococcus aureus. Conversely, S. epidermidis also has a beneficial role in balancing the microflora on human epithelial surfaces by controlling outgrowth of harmful bacteria such as in particular S. aureus. Recent research yielded detailed insight into key S. epidermidis virulence determinants and their regulation, in particular as far as biofilm formation is concerned, but we still have a serious lack of understanding of the in vivo relevance of many pathogenesis mechanisms and the factors that govern the commensal life of S. epidermidis.