Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease which predominantly affects children usually clearing up during or after childhood. However, AD may persist with a chronic recurrent course until adulthood, being recalcitrant to any treatment strategy. Moreover, in some patients AD is not present during childhood but starts later in life (i.e. after 16 years of age) being defined late-onset AD. Even if AD incidence is increasing worldwide with cases in which clinical manifestations first appeared or persisted during adolescence and adulthood raising, especially in industrialized countries, studies on adult AD are still scant. Since this subgroup of AD patients often has a nonflexural rash distribution, and atypical morphologic variants and validated diagnostic criteria are lacking, there is no clear consensus on the diagnostic work-up that should be performed when evaluating adult patients with AD. In this review the many aspects of work-up in adult patients with AD, such as diagnostic criteria, epidemiology, quality of life and pathogenesis are discussed.