Atopic dermatitis is characterized by the interplay of skin barrier defects with the immune system and skin microbiome that causes patients to be at risk for infectious complications. This article reviews the pathogenesis of atopic dermatitis and the mechanisms through which patients are at risk for infection from bacterial, viral, and fungal pathogens. Although these complications may be managed acutely, prevention of secondary infections depends on a multipronged approach in the maintenance of skin integrity, control of flares, and microbial pathogens.