Atopic dermatitis (AD) is a common dermatologic disease that can occur at different ages with different clinical manifestations. The etiologic factors and the pathogenetic pathways of AD have been thoroughly investigated but as often happens, something more has to be yet elucidated before the statement, that we possess the overall comprehension of the disease, could be considered the truth. Treatment of AD is often challenging, because of the chronic course of the disease and the fact that even the best of therapies is affected by adverse events, intolerances, or the possible occurrence of contraindications resulting from a sudden change in the overall health status of the patient (e.g., the onset of some comorbidities). Hence, the need to know "how, when, with what, and why" to treat AD patients with the many therapeutic modalities is now in the hands of the dermatologists.