Atopic diseases are heterogeneous. Alongside atopic dermatitis (AD), they include allergic asthma, allergic rhinitis and nasal polyposis, atopic ocular surface diseases (keratoconjunctivitis), IgE-mediated food allergies, and eosinophilic esophagitis. With the development of targeted treatments, the current management of AD, based on a single algorithm common to all patients, is less suited for managing patients with varied atopic profiles. This article discusses systemic therapeutic options based on the atopic comorbidities associated with AD. For instance, in comorbid asthma, dupilumab is currently the only biologic indicated for patients with moderate to severe AD and severe asthma. It is the preferred biotherapy for patients with a dual severe phenotype, both cutaneous and respiratory. However, the asthma phenotypes classically associated in our patients with moderate to severe AD are most often mild to moderate and controllable with inhaled treatments. Therefore, the use of biotherapy targeting IL-13 or JAK inhibitors remain recommended for the treatment of AD in this context, similarly to dupilumab.