Atopic dermatitis (AD) is a chronic, inflammatory, pruritic skin disease with increasing prevalence. The etiopathogenesis of atopic dermatitis is multifactorial and involves a complex interplay of environmental and genetic factors that induce derangements in the structure and function of the epidermal barrier and immune system. Due to great heterogeneity of etiopathogenesis, there is also great variability of clinical presentation, and diagnosis can sometimes be challenging and difficult. Diagnosis mostly relies on clinical features and laboratory tests, but morphology alone cannot reliably establish the diagnosis, so the spectrum of features associated with AD must be considered. Traditionally, patients with AD have been separated into two different subgroups, i.e. intrinsic and extrinsic. Today, most of authors prefer the outside to inside and back to outside hypothesis, suggesting that the primary disorder lies in epidermal structure and function, resulting in inflammation and immunological downstream activation which further provokes secondary barrier abnormalities. In this review, we discuss the structure and function of the epidermal barrier and the role of impaired barrier function in etiopathogenesis of atopic dermatitis.