Heart failure is a common form of heart disease associated with progressive exercise intolerance and high risk of adverse clinical outcome events. The pathophysiology of chronic systolic heart failure is fundamentally determined by the failure of the circulatory system to deliver oxygen sufficient for metabolic needs, and it is best explained by a complex interplay between intrinsic abnormalities of ventricular pump function and extracardiac factors that limit oxygen use in metabolically active tissues. This brief review highlights the role of extracardiac factors (peripheral factors) that may impact exercise capacity in patients with chronic systolic heart failure. Reduced metabolic vasodilation limits delivery of available cardiac output reserve to skeletal muscle during exercise, and it is associated with reduced peak oxygen capacity. Abnormal substrate use in skeletal muscle due to reduced skeletal muscle mass, change in skeletal muscle fiber type, and mitochondrial dysfunction reduces work efficiency and submaximal exercise endurance capacity in patients with systolic heart failure. These extracardiac peripheral mechanisms of impaired exercise tolerance in chronic heart failure may be targets for novel therapeutic development in this patient population.