During exercise nervous signals are generated by stimulation of mechanically (muscle mechanoreflex) and chemically (muscle metaboreflex) sensitive skeletal muscle receptors. These receptors and their associated afferent fibres are sensitive to muscle work and reflexively adjust the haemodynamic, ventilatory and circulatory responses during physical effort. Thus the muscle reflex is essential in achieving normal responses to exercise in healthy subjects. In chronic heart failure, characterised by exercise intolerance with early occurrence of dyspnea or fatigue, peripheral muscle abnormalities (i.e. muscle atrophy, decreased peripheral blood flow, fibre-type transformation, and reduced oxidative capacity) trigger an exaggerated muscle reflex. This abnormality has recently been implicated in the genesis of the disabling symptoms. We review the role of the muscle reflex in regulating the cardiovascular and the ventilatory systems during exercise in both healthy and diseased conditions.