Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder that affects approximately 15% of children in the United States. A complex disorder, AD is characterized by both skin barrier impairment and immunologic abnormalities, including decreased innate immune function and a polarized adaptive immune response. Mouse models have demonstrated the complex interdependence of immune cell-keratinocyte interactions and teased apart gene-environment relationships in a controlled setting. In this issue, Nagelkerken et al. present a mouse model with transgenic expression of apolipoprotein C1 that disrupts the skin lipid barrier and manifests many hallmark features of AD.