• This review focuses on the relations between neural structures and the heart in the pathogenesis of severe cardiac dysfunction (namely, cardiac arrhythmias, focal cardiac lesions, and the sudden death syndrome). After establishing the anatomic connections between the brain and the heart and then reviewing ways to assess the integrity of nerves to the heart, the clinical literature relating human brain dysfunction to cardiologic problems is reviewed. Next the experimental literature is briefly reviewed. The organization of the information is based on whether or not the heart of the experimental animal is normal as well as on the part of the nervous system involved (ie, either central or peripheral). In addition, since the effect of environmental stress on cardiac dysfunction must be modulated via the brain, the review is briefly extended to examine the role of stress in the production of severe cardiac dysfunction in people as well as animals.