Staphylococcus aureus is a bacterial species with pathogenic potential to both humans and animals. The primary natural niche is said to be the human vestibulum nasi from where bacterial cells may spread to the environment or additional anatomical sites such as the perineum or the hands, where residence is usually transient. Apparently, S. aureus is capable of a precise and balanced interaction with specific types of eukaryotic nasal cells. Although a wide variety of important bacterial ligands and possible eukaryote receptors have been described, the precise mechanisms leading to persistent bacterial colonization and, even more importantly, associated infection have not yet been elucidated in detail. This may be a consequence of the fact that most of the adherence factors have been studied individually in simplified in vitro systems, not taking the complexity of multi-factorial in vivo cell-cell interactions into account. An overall scheme of the initial and sequential interactions leading to S. aureus colonization of eukaryotic cell surfaces has not yet emerged. This review concisely describes the current state of affairs in the multi-disciplinary field of staphylococcal adherence research. Specific emphasis is placed upon the pros and cons of the various artificial, mostly in vitro models employed to study the interaction between bacterial and human or animal cells.