Atopic dermatitis (AD) is a multifactorial, heterogeneous disease characterized by epidermal barrier dysfunction, immune system dysregulation, and skin microbiome alterations. Skin microbiome studies in AD have demonstrated that disease flares are associated with microbial shifts, particularly Staphylococcus aureus predominance. AD-associated S. aureus strains differ from those in healthy individuals across various genomic loci, including virulence factors, adhesion proteins, and proinflammatory molecules—which may contribute to complex microbiome barrier–immune system interactions in AD. Different microbially based treatments for AD have been explored, and their future therapeutic successes will depend on a deeper understanding of the potential microbial contributions to the disease.