Chronic obstructive pulmonary disease (COPD) and asthma are two of the most common chronic diseases worldwide. Both diseases are heterogenous and complex, and despite their similarities, they differ in terms of pathophysiological and immunological mechanisms. Mounting evidence supports the presence of several phenotypes with various responses to treatment. A systematic and thorough assessment concerning the diagnosis of both asthma and COPD is crucial to the clinical management of the disease. The identification of different biomarkers can facilitate targeted treatment and monitoring. Thanks to the presence of numerous immunological studies, our understanding of asthma phenotypes and mechanisms of disease has increased markedly in the last decade, and several treatments with monoclonal antibodies are available. There are compelling data that link eosinophilia with an increased risk of COPD exacerbations but a greater treatment response and lower all-cause mortality. Eosinophilia can be considered as a treatable trait, and the initiation of inhaled corticosteroid in COPD patients with eosinophilia is supported in many studies. In spite of advances in our understanding of both asthma and COPD in terms pathophysiology, disease mechanisms, biomarkers, and response to treatment, many uncertainties in the management of obstructive airways exist.