Asthma and chronic obstructive pulmonary disease (COPD) affect more than 40 million Americans, cost more than $100 billion annually, and together constitute the fourth-leading cause of death in the United States. Distinguishing between asthma and COPD can be difficult; accurate diagnosis requires spirometry that demonstrates a characteristic pattern. Asthma is diagnosed if airway obstruction on spirometry is reversible (greater than 12% and greater than 200 mL improvement in forced expiratory volume in one second [FEV₁]) with administration of bronchodilators or through the observation of bronchoconstriction (reduction in FEV₁ of 20% or greater) with a methacholine challenge. COPD is diagnosed if airway obstruction (FEV₁/forced vital capacity [FEV₁/FVC] ratio less than 70%) on spirometry is not reversible with bronchodilators. Although not considered a separate diagnosis, asthma-COPD overlap can be a useful clinical descriptor for patients displaying diagnostic features of both diseases. In these cases, spirometry will show reversibility after administration of bronchodilators, which is consistent with asthma, and the persistent baseline airflow limitation that is more characteristic of COPD. Treatment should follow Global Initiative for Asthma guidelines and Global Initiative for Chronic Obstructive Lung Disease guidelines. In patients with asthma-COPD overlap, pharmacotherapy should primarily follow asthma guidelines, but pharmacologic and nonpharmacologic approaches specific to COPD may also be needed.