The autonomic nervous system plays an integral role in homeostasis. Autonomic modulation can frequently be altered in critically ill patients. Assessment of heart rate variability (HRV) 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 HRV may occur over a broad range of critical illness and injury and may be inversely correlated with disease severity and outcome has been tested in the last decade. In this article, we review recent literature concerning assessment of HRV in patients with critical illness or injury, as well as the potential clinical implications and limitations of HRV assessment in this area.