The recent definition that chronic obstructive pulmonary disease (COPD) is a “preventable and treatable disease state characterized by airflow limitation that is not fully reversible” reminds that the respiratory functional evaluation is an integral part in the diagnostic and follow-up process in this disease. This review has the scope to focus on some of the most debated pathophysiological and functional issues. One of these is how airflow obstruction occurs and progresses. To this aim, we will discuss the functional role of mucus, increased thickness of the submucosa and adventitia, airway smooth muscle, site of airway narrowing, collapsibility of the central airways, and loss of lung elastic recoil in decreasing flow. Then, we will present a functional clinical approach to the disease that covers the most important features of the disease, such as diagnosis, follow-up, severity assessment, lung hyperinflation, and bronchodilator response.