In 1981 a study on heart rate variability (HRV) and on the neural control of the heart was published in Science. Since then, the number of papers concerning this topic has increased exponentially. Some aspects of the relationship between HRV and the neural control of the cardiovascular system are now clear, for example: a decreased SDNN (a measure of variance) during a period of 24 hours is a well established independent negative prognostic factor after acute myocardial infarction and in chronic heart failure patients. Moreover, an increased sympathetic modulation elicited by standard laboratory maneuvers determines an increased power of the low frequency (LF) spectral component (0.03-0.15 Hz), expressed in normalized units. Nevertheless, the interpretation of the oscillatory components present in HRV, particularly in pathophysiological conditions, is far from being clear. The influence of several neurohumoral circuits can induce various changes in HRV according to different physiological or pathological conditions. A new approach to the study of HRV called "information domain" might help to obtain some more information about HRV. Furthermore, in the future, HRV analysis might be useful when deciding on the best pharmacological combination for the individual patient and for the probabilistic prediction of acute cardiac events.