Abstract Atopic dermatitis (AD) and food allergy (FA) frequently manifest during infancy and share skin barrier dysfunction as a critical early pathogenic event. Recent research has elucidated structural, lipidomic, microbial, and immunologic abnormalities that compromise the skin barrier and contribute to disease onset. Filaggrin gene mutations, altered ceramide profiles, and type 2 cytokine–driven inflammation are among the key factors disrupting epidermal integrity. While AD and FA exhibit overlapping features, including elevated risk in the presence of skin barrier defects, their pathophysiologic pathways are more complicated. This review provides updated evidence on the role of the skin barrier in the pathogenesis of AD and FA. It further highlights the distinction between these conditions and discusses recent findings from birth cohorts and interventional trials. In AD, early emollient application and environmental control show limited but promising preventive effects, particularly in high‐risk infants. In FA, prevention strategies should also address the induction of oral immune tolerance through timely introduction of allergenic foods. Future research should focus on refining predictive biomarkers, validating stepwise interventions, and developing safe, barrier‐based strategies that integrate both prevention and treatment to reduce the burden of AD and FA from early life. image