Autonomic nervous system plays an integral role in homeostasis. Autonomic modulation can frequently be altered in patients with cardiac disorders as well as in patients with other critical illnesses or injuries. Assessment of heart rate variability is based on analysis of consecutive normal R-R intervals and may provide quantitative information on the modulation of cardiac vagal and sympathetic nerve input. The hypothesis that depressed heart rate variability may occur over a broad range of illness and injury, and may inversely correlated with disease severity and outcome has been tested in various clinical settings over the last decade. This article reviews recent literature concerning the potential clinical implications and limitations of heart rate variability assessment in general medicine.