The Gram-positive bacterium Staphylococcus aureus is a wide spread opportunistic pathogen that can cause a range of life-threatening diseases. To obtain a better understanding of the global mechanisms for pathogenesis and to identify novel targets for therapeutic interventions, the S. aureus proteome has been recently ‘dissected’ in several studies. Proteins that are exposed on the cell surface – collectively referred to as the ‘surfacome’ – have received particular attention, because they can directly interact with extracellular molecules, including drugs and antibodies. Accordingly, these proteins represent interesting candidate targets for active or passive immunization against S. aureus. Here, we review the proteomics strategies used, and we compare the results that were so far obtained. Since the surfacome is part of the cell wall proteome, we first present an overview of general properties of the S. aureus cell envelope, cell wall-associated proteins and mechanisms for protein attachment to the cell wall. Then we zoom in on the surfacome, and discuss the pro's and con's of the specific strategies that have been applied for surfacome profiling. The insights thus obtained may serve as leads for future studies on the S. aureus surfacome and possible applications.