Atopic dermatitis (AD) is a paradigmatic inflammatory chronic skin disease. As for other chronic skin diseases, (i) the spectrum of the clinical phenotype and severity as well as (ii) the genetic background and (iii) the underlying mechanisms strongly suggest a high degree of pathophysiological heterogeneity yet leading to a similar clinical pattern, that is, the eczematous skin lesion, but showing distinct progression patterns. This review suggests to exploit the recent knowledge about AD for a novel approach proposing a tentative first molecular taxonomy of this disease based on the genotype and endophenotype. The consequences in terms of personalized prevention and management are delineated.