Staphylococcus aureus is frequently isolated from the skin of atopic dermatitis (AD) patients during flares. The normal microbiota is disrupted and the diversity of the microorganisms on the skin is reduced. Many species that produce inhibitors of S. aureus growth decline. Strains from S. aureus clonal complex 1 are enriched among AD sufferers whereas the CC30 strains most frequently isolated from nasal carriers in the normal population are much rarer in AD. S. aureus expresses several molecules that contribute to the intensity of symptoms, including δ-toxin which stimulates mast cells, α-toxin which damages keratinocytes, phenol-soluble modulins which stimulate cytokine release by keratinocytes, protein A which triggers inflammatory responses from keratinocytes, superantigens which trigger B cell expansion and cytokine release, and proinflammatory lipoproteins. Proteases contribute to disruption of the epidermal barrier. S. aureus isolated from AD patients adheres to the deformed corneocytes from AD patients in a clumping factor B-dependent fashion. Novel targeted therapies for AD have recently been introduced to clinical practice with many more in development, including monoclonal antibodies that specifically target cytokines and their receptors, and a bacteriophage lysin that eliminates S. aureus from AD skin.