Allergy is on the rise worldwide. The hygiene hypothesis of atopic diseases linked microbes with atopic dermatitis (AD) both as drivers and modulators of skin pathology. The earlier literature favoured an inside–outside model of AD where an immunological abnormality compounded by a gut microbiota dysbiosis is the primary event. Probiotic intervention trials with lactobacilli and bifidobacteria as well as the application of bifidogenic oligosaccharide prebiotics showed indeed promising clinical results, but no consistent gut microbiota dysbiosis could be linked with AD. An alternative hypothesis known as outside–inside model of AD considers a genetic skin barrier effect compounded by a skin microbiota dysbiosis as primary pathogenic event. Cultivation microbiology has demonstrated strong skin colonization with superantigen-encodingStaphylococcus aureusin AD patients; microbiota and molecular microbiome analyses demonstrated thatS. aureusabundance fluctuates and parallels clinical symptoms. In a mouse model, δ-toxin ofS. aureusinduced mast cell degranulation, leading to AD-like symptoms. Mutant mice developing AD symptoms showed increased skin colonization withS. aureus; antibiotic treatment alleviated the symptoms. Clinical trials showed that various treatments reducingS. aureusskin load also reduced AD symptoms, suggestingS. aureusas a potential critical driver of AD and a target for antimicrobial interventions other than antibiotics.