The prevalence of atopic dermatitis is increasing in western societies and this disease has a significant effect on the quality of life of patients and their families. The pathophysiology is complex, but there are recent insights on innate and adaptive immunity dysfunction in this condition that increases the predisposition to colonization/infection with characteristic types of microorganisms. We provide an up-to-date review of the pathophysiology of atopic dermatitis, highlighting the clinical implications of skin barrier dysfunction and immunological deregulation. We suggest a useful approach for handling exacerbations and infectious events.