Sympathetic-parasympathetic interaction plays a major role in the evolution and outcome of many cardiovascular disorders. Nonetheless, a thorough understanding of this relationship and of its potential implications for prognosis and management still escapes many cardiologists. This article reviews the background of sympathetic-parasympathetic interactions focusing on the best direct evidence available, namely direct neural recordings of the activity of single vagal and sympathetic fibers directed to the heart. It examines indirect but highly reliable markers of this interaction as they can be studied in the clinical setting of ischemic heart disease and of heart failure, focusing primarily on the experimental and clinical studies of baroreflex sensitivity. It concludes by drawing inferences likely to lead to a novel approach to the management of heart failure, resulting from the knowledge gained about the vagal control of the heart and based on electrical vagal stimulation.