The brain controls the heart directly through the sympathetic and parasympathetic branches of the autonomic nervous system, which consists of multi-synaptic pathways from myocardial cells back to peripheral ganglionic neurons and further to central preganglionic and premotor neurons. Cardiac function can be profoundly altered by the reflex activation of cardiac autonomic nerves in response to inputs from baro-, chemo-, nasopharyngeal and other receptors as well as by central autonomic commands, including those associated with stress, physical activity, arousal and sleep. In the clinical setting, slowly progressive autonomic failure frequently results from neurodegenerative disorders, whereas autonomic hyperactivity may result from vascular, inflammatory or traumatic lesions of the autonomic nervous system, adverse effects of drugs and chronic neurological disorders. Both acute and chronic manifestations of an imbalanced brain–heart interaction have a negative impact on health. Simple, widely available and reliable cardiovascular markers of the sympathetic tone and of the sympathetic–parasympathetic balance are lacking. A deeper understanding of the connections between autonomic cardiac control and brain dynamics through advanced signal and neuroimage processing may lead to invaluable tools for the early detection and treatment of pathological changes in the brain–heart interaction.