The complex nature of interactions between the pulmonary and cardiovascular systems is becoming increasingly appreciated. Pulmonary vascular abnormalities are frequently present in patients with respiratory disorders, including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, sarcoidosis, neuromuscular or chest wall disorders, and disorders of ventilatory control including sleep apnea syndromes and obesity hypoventilation syndrome. Pulmonary hypertension, classified as group III in the World Health Organization classification scheme for pulmonary hypertension, may result in severe right ventricular dysfunction caused by lung disease, also known as cor pulmonale. The development of cor pulmonale is generally associated with poorer prognosis and increased death. Systemic manifestations of lung disease, particularly obstructive disorders, are also particularly relevant because they are associated with increased cardiac death and impaired health status. This article will discuss the most common pulmonary diseases and disorders of ventilatory control that cause pulmonary vascular abnormalities and cor pulmonale, with particular concentration on how treatment of these diseases may affect the heart. In addition, the complex nature of cardiac and lung disease will also be explored, particularly with respect to the relationship between chronic obstructive pulmonary disease, systemic inflammation, atherosclerosis, and cardiovascular death, which is currently a very active focus of research.