Atopic dermatitis (AD) is a heterogeneous disease with unique clinical manifestations across age groups and race/ethnicities. Characteristic molecular mechanisms, known as endotypes, including IgE level, status of epidermal barrier genes, and differential cytokine axes activation in the background of T 2 upregulation, are also implicated. In adults, the T 22, T 17, and T 1 pathways are involved, and a weakened epidermal barrier is characteristic. In contrast, pediatric patients exhibit less T 1 activation, and defects in epidermal lipid metabolism contribute to their barrier defect. European American patients are characterized by higher differential T 2/T 22 activation, lower expression of the T 1/T 17 axes, and suppression of filaggrin (FLG) and loricrin gene expressions. Asian patients have accentuated polarity of the T 22/T 17 pathways, and also exhibit epidermal barrier defects despite relative maintenance of FLG and loricrin expression. African American patients do not exhibit FLG mutations and have distinct attenuation of T 17/T 1 axes activation. Dissecting the molecular basis of AD endotypes has provided an important framework upon which targeted therapeutics are being developed. An increased understanding of these subtypes and the alteration of biomarkers that correlate with disease can ultimately push AD treatment in an era of personalized medicine.