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Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense pruritus and xerosis. AD pathogenesis is multifactorial, involving genetic, environmental, and immunological factors, including the participation of <i>Staphylococcus aureus</i>. This bacterium colonizes up to 30&#8722;100% of AD skin and its virulence factors are responsible for its pathogenicity and antimicrobial survival. This is a concise review of <i>S. aureus</i> superantigen-activated signaling pathways, highlighting their involvement in AD pathogenesis, with an emphasis on skin barrier disruption, innate and adaptive immunity dysfunction, and microbiome alterations. A better understanding of the combined mechanisms of AD pathogenesis may enhance the development of future targeted therapies for this complex disease.