Exertional intolerance is a major clinical problem in ambulatory patients with chronic heart failure and is associated with both muscle fatigue and dyspnea. The increased muscle fatigability is most likely caused by a combination of muscle underperfusion and muscle deconditioning; patients frequently exhibit skeletal muscle atrophy, altered muscle metabolism and reduced mitochondrial-based enzyme levels, consistent with deconditioning. The muscle underperfusion is largely due to impaired arteriolar vasodilation within exercising muscle. Exertional dyspnea appears to be due to increased respiratory muscle work mediated by excessive ventilation and decreased lung compliance. Both excessive carbon dioxide production, secondary to increased muscle lactate release, and increased lung dead space contribute to the excessive ventilation. Decreased lung compliance is caused by chronic pulmonary congestion and fibrosis. Optimal management of exercise intolerance in patients with heart failure requires an understanding of the role of these multiple potential contributors to exertional fatigue and dyspnea.