Bronchial asthma is a chronic airway inflammatory disease of the respiratory tract that varies in terms of clinical presentations (phenotypes) and distinct underling pathophysiological mechanisms (endotypes). The definition of phenotype/endotype is crucial tak-ing into account the availability of novel biologic agent dedicated to patients who do not respond to conventional therapies. Although patients suffering from type 2 severe asthma significantly benefit from treatment with biologics no responders patients have been identified. Comorbidities increase the symptoms of asthma and complicate the overall management of the disease. The assessment and treatment of comorbidities is a crucial step and they the appropriate management may improve asthma symptoms and morbidity. Among comorbidities certainly chronic rhinosinusit with nasal polyps, obesity, bronchiectasis and immune defects represent a group of clinical conditions that negatively impact on asthma control despite a correct treatment. Although asthma is frequently characterized by an increase of blood eosinophils that releasing mediators and cytokines are involved in the inflammatory processes of airways wall, in patients with very high blood eosinophil levels it is opportune to be very careful in discerning whether it is a case of isolated severe eosinophilic asthma or a case of asthma in EGPA disease. In addition, hypereosinophilia can be the consequence of specific biological treatment as in the case of dupilumab. In this paper we have outlined the clinical features of those patients with severe asthma in which the management of the disease can be more complex.