Atopic dermatitis (AD) is a chronic inflammatory skin disease with a steadily increasing prevalence affecting 10%-20% of infants and 1%-3% of adults globally. It is often the first clinical manifestation of atopic disease preceding asthma and allergic rhinitis. At least half of the children with AD develop some other form of atopic disease later in life. The pathogenesis of AD involves a complex interplay of factors, including genetic predisposition due to altered immune or skin barrier function, interactions with the environment, and infectious triggers of inflammation. In this review, we summarize the recent advances in understanding the contribution of different factors in the pathophysiology of AD in human and animal model systems. These insights provide new therapeutic potential for the treatment of human AD.