Staphylococcus aureus is a major pathogen in both community and hospital settings. It is a significant etiological agent to treat in healthcare-related infections due to both its ability to cause invasive infection as well as to form biofilm on biomaterials and the high prevalence of resistance to first line antibiotics. The most challenging preventive strategy is vaccine development to guarantee a full and durable protection from staphylococcal diseases in all different high-risk populations, even if the lack of a known correlate of protection from S. aureus is a major hindrance to this effort. We aimed to review the most recent advances in the field of vaccinology against S. aureus, highlighting the potential for future application of the different experimental vaccine types. Several vaccines have completed their preclinical phase of development and others have been tested in humans, however no successful phase III clinical trial has yet been completed.