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<i>Staphylococcus aureus</i>, a prevalent human pathogen and a leading cause of hospital-acquired infections, is increasingly evolving antibiotic-resistant strains, increasing mortality and morbidity rates. Anti-staphylococcal vaccine research for prevention and treatment has become a priority. Antibodies against specific <i>S. aureus</i> components, toxins, and polysaccharides have demonstrated encouraging results in animal studies regarding protection against colonization or infection. However, human immunization trials have yielded less optimistic outcomes, with no anti-staphylococcal having passed clinical trials up to now. Although multiple formulation attempts triggered strong antibody responses, the vaccines could not effectively prevent <i>S. aureus</i> infections. This article delves into the results of immunotherapeutic strategies against <i>S. aureus</i> in both animal and human studies, discussing the feasibility of adequate immunization approaches against <i>S. aureus</i> in humans.