The natural course of chronic obstructive pulmonary disease (COPD) is complicated by the development of systemic consequences and comorbidities. COPD has been associated with an increased risk for cardiovascular disease, osteoporosis, cachexia and skeletal muscle weakness. In several large prospective cohort studies, the degree of airflow limitation was an independent predictor of both fatal and nonfatal cardiovascular events, implying a causal relationship between airflow obstruction and vascular disease. The pathomechanisms responsible for this association are mostly unknown. It has been proposed that systemic inflammation, oxidative stress, hypoxia and sympathetic activation may be mechanisms in COPD leading to vascular dysfunction and cardiovascular disease. However, the current evidence of a causal relationship between COPD and vascular dysfunction is insufficient and more data from well-designed studies are urgently needed, hopefully leading to novel therapeutic and preventive approaches in the care of patients with COPD.