Summary In heart failure (HF) strong haemodynamic and neuronal signalling feedback interactions between the heart and the central nervous system (CNS) exist that are able to mutually provoke acute or chronic functional impairment. Cerebral injury secondary to HF may include acute stroke, cognitive decline and dementia and depressive disorders. Also brain stem functions are involved in the cardiac-cerebral interaction in HF as neurohormonal control and neuronal reflex circuits are known to be impaired or imbalanced in HF. In turn, impaired cerebral functions may account for direct and indirect myocardial injury and may contribute to symptomatic severity of HF, to disease progression and to increased mortality. Despite the clinical and pathophysiologic significance of the heart—CNS interaction, this relevant field of HF comorbidity is clinically under-recognized with regard to both diagnostic workup and treatment efforts. Here, principal aspects of pathophysiologic heart—CNS interactions related to HF are discussed such as stroke, effects on cognitive function, on depressive disorder and neurovegetative control and neuronal cardiovascular reflex regulation. Aspects of (limited) treatment options for cerebral functional interactions in HF are examined.