This review presents recent evidence of impaired Notch signalling in atopic dermatitis (AD), which is proposed to represent the "a-topic" defect linking both epidermal and immunological barrier dysfunctions in AD. AD epidermis exhibits a marked deficiency of Notch receptors. Mouse models with genetically suppressed Notch signalling exhibit dry skin, signs of scratching, skin barrier abnormalities, increased transepidermal water loss and TH2 cell-mediated immunological changes closely resembling human AD. Notch signals are critically involved in the differentiation of regulatory T cells, in the feedback inhibition of activated innate immunity, in late epidermal differentiation associated with filaggrin- and stratum corneum barrier lipid processing. Most importantly, Notch deficiency induces keratinocyte-mediated release of thymic stromal lymphopoietin (TSLP). TSLP promotes TH2 cell-driven immune responses associated with enhanced production of interleukin (IL)-4 and IL-31. Both TSLP and IL-31 stimulate sensory cutaneous neurons involved in the induction of itch. Notably, Notch1 is a repressor of activator protein-1 (AP-1), which is upregulated in AD epidermis. Without Notch-mediated suppression of AP-1 this transcription factor promotes excess expression of TH2 cell-related cytokines. Impaired Notch signalling negatively affects the homeostasis of aquaporin 3 and of the tight junction component claudin-1, thus explains disturbed skin barrier function with increased transepidermal water loss and Staphylococcus aureus colonisation as well as increased cutaneous susceptibility for viral infections. Thus, accumulating evidence links deficient Notch signalling to key pathological features of AD.