Chronic obstructive pulmonary disease (COPD) is a spectrum of various syndromes that share airflow limitation but differ in many respects. Although airflow limitation is a defining element of COPD, forced expiratory volume in 1 s (FEV 1) alone is not sufficient to explain the heterogeneity of COPD. Phenotypic characterization of clinically relevant subgroups of COPD will increase our understanding of COPD. Furthermore, a greater understanding of the complex interrelationships between the phenotypes and their environmental, genetic, molecular, and cellular basis may be achieved with comprehensive and integrated method (systems biology and network medicine). Incorporation of information obtained from these analyses into our clinical practice would allow clinicians to treat individual patients with so-called Personalized, Predictive, Preventive, and Participatory (P4) medicine. By understanding COPD heterogeneity, it may be possible in the future to detect the disease earlier and to target treatment to reduce mortality and modify the course of the disease.