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Vaccination arguably remains the only long-term strategy to limit the spread of <i>S. aureus</i> infections and its related antibiotic resistance. To date, however, all staphylococcal vaccines tested in clinical trials have failed. In this review, we propose that the failure of <i>S. aureus</i> vaccines is intricately linked to prior host exposure to <i>S. aureus</i> and the pathogen’s capacity to evade adaptive immune defenses. We suggest that non-protective immune imprints created by previous exposure to <i>S. aureus</i> are preferentially recalled by SA vaccines, and IL-10 induced by S. aureus plays a unique role in shaping these non-protective anti-staphylococcal immune responses. We discuss how <i>S. aureus</i> modifies the host immune landscape, which thereby necessitates alternative approaches to develop successful staphylococcal vaccines.