Staphylococcus aures are prominent members of the normal flora of humans and animals, but are also a major cause of mild and severe infections. To persist and disseminate in the human host, and to survive in environmental settings, such as hospitals, S. aureus have developed a plethora of cellular stress responses allowing it to sense and adapt to its very different niches. The stress responses often involve dramatic cellular reprogramming, and the technological advances provided by the access to whole genome sequences have let to an unprecedented insight into the global reorganization of gene and protein expression following stress-exposure. Characterization of global gene responses has been very helpful both in identifying regulators sensing specific environmental stress signals and overlaps between different stress responses. In this chapter we review the recent progress in our understanding of the specific and general S. aureusstress responses, with a special emphasis on how stress responses contribute to virulence and antibiotic resistance in this important human pathogen.