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Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous syndrome that represents a major global health burden. COPD phenotypes have recently emerged based on large cohort studies addressing the need to better characterize the syndrome. Though comprehensive phenotyping is still at an early stage, factors such as ethnicity and radiographic, serum, and exhaled breath biomarkers have shown promise. COPD is also an immunological disease where innate and adaptive immune responses to the environment and tobacco smoke are altered. The frequent overlap between COPD and other systemic diseases, such as cardiovascular disease, has influenced COPD therapy, and treatments for both conditions may lead to improved patient outcomes. Here, we discuss current paradigms that center on improving the definition of COPD, understanding the immunological overlap between COPD and vascular inflammation, and the treatment of COPD—with a focus on comorbid cardiovascular disease.