The prevalence and disease burden of atopic dermatitis (AD) is substantial. AD causes significant impairment in quality of life. It is also associated with mental disorders as well as cardiovascular diseases. Many factors including race, environment, skin barrier dysfunction, immune regulatory abnormalities, and microbiome have been reported to affect the pathophysiology of AD. A variety of cell types including Th2, Th17, Th22, and type 2 innate lymphoid cells contribute to AD. Cytokines from these immune cells cause abnormal epidermal differentiation and skin barrier dysfunction. Moreover, microbial dysbiosis and deficiency of antimicrobial peptides result in Staphylococcus aureus infection. Recently, new drugs have been successfully launched to target polarized immune pathways that lead to moderate-to-severe AD.