These findings underscore the importance of understanding the complex interactions of multiple-organ systems in a chronic systemic disease state like congestive heart failure. The exaggerated ventilatory response in patients with heart failure is clearly multifactorial and it remains difficult to decipher whether this response results from or contributes to the sensation of dyspnea. Pulmonary dysfunction including ventilation-perfusion mismatching, decreased lung compliance, restriction, airway obstruction, decreased diffusion capacity, and decreases in respiratory muscle strength and endurance contribute to an inefficient breathing pattern and increased work of breathing. This is further compounded by the limited ability of the failing heart to meet the metabolic demands of the respiratory muscles, leading to under-perfusion and ischemia. This imbalance contributes to perceived dyspnea and exercise limitations. Understanding these physiologic cardiopulmonary interactions may lead to therapeutic modalities, such as respiratory muscle training, aimed at disrupting this intertwined cycle of events and improving functional capacity in patients with heart failure.