Atopic dermatitis (AD) is a chronic inflammatory disease associated with genetic and environmental factors. Complex genetic predispositions related with epidermal barrier dysfunction and dysregulation of innate and adaptive immunity play a key role in the pathogenesis of AD. The two-three fold increase in the incidence of AD among developed countries in the last decade cannot be explained merely with genetic predispositions. An increasing number of genetic studies in recent years have reported the likely association between AD and abnormal epigenetic regulation of the epidermal barrier and immune system mediated by environmental factors. However, there still remain many issues that are unclear. The causes of the phenotypic heterogeneity in AD and the mechanisms through which environmental and developmental factors interacting with genetic factors affect the individual susceptibility to the disease are the main issues that need to be elucidated.