Aim:Global and regional data have shown that chronic airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma are increasing in incidence and prevalence, with detrimental consequences to healthcare resources and the quality of life of patients. A firm diagnosis of COPD or asthma is important because the natural history, treatment, and outcomes differ between the two respiratory diseases. The aim of this review is to provide nurse practitioners (NPs) with the requisite facts to understand and improve the diagnosis and treatment of affected individuals.Methods:Articles on the differential diagnosis, treatment, and management of COPD and asthma published in peer-reviewed journals were retrieved from PubMed. Evidence-based respiratory guidelines, World Health Organization disease-related data, and US prescribing information for different respiratory medications served as additional data sources.Conclusions:NPs, along with other primary care professionals, form the frontline in diagnosing, treating, and managing COPD and asthma. Differentiating COPD from asthma has prognostic as well as significant therapeutic implications. Since NPs play a key role in diagnosing and managing patients with COPD and asthma, those with a comprehensive understanding of the diagnostic and therapeutic differences between the two diseases can help to lower the risks of exacerbations and hospitalizations, and improve the quality of life of these patients.