Heart failure (HF) is a complex syndrome characterized by myocardial dysfunction and a poor prognosis. Among multiple markers of severity, an exercise ventilation inefficiency has important clinical and prognostic value. The pathophysiology determining exercise ventilatory inefficiency is complex and not definitively clarified. Three different mechanisms have been identified: (i) increased dead space, (ii) early occurrence of lactic acidosis, and (iii) abnormal chemoreflex and/or metaboreflex activity. Besides its prognostic value, abnormal ventilation can be influenced by pharmacological and non-pharmacological therapies such as beta-blockers, selective cyclic 3'-5' guanosine monosphosphate phosphodiesterase inhibitors, physical training, and nocturnal continuous positive airway pressure. There is an increasing interest for the exercise periodic breathing, which is frequently associated with HF syndrome and has prognostic importance. The precise mechanisms sustaining exercise periodic breathing are not fully defined but ventilatory and metabo-haemodynamic hypotheses have been proposed.