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 . This bacterium colonizes up to 30-100% of AD skin and its virulence factors are responsible for its pathogenicity and antimicrobial survival. This is a concise review of 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.