Chronic obstructive pulmonary disease (COPD) is a complex disease manifested primarily as airflow limitation that is partially reversible as confirmed by spirometry. COPD patients frequently develop systemic manifestations, such as skeletal muscle wasting and cachexia. COPD patients often develop other comorbid diseases, such as ischemic heart disease, heart failure, osteoporosis, anemia, lung cancer, and depression. Comorbidities complicate management of COPD and need to be evaluated because detection and treatment have important consequences. Novel approaches aimed at integrating the multiple morbidities seen in COPD and other chronic diseases will provide new avenues of research and allow developing more comprehensive and effective therapeutic approaches.