Research on heart rate variability (HRV) has been conducted for more than four decades, and the increasing interest in this complex psychophysiological phenomenon continues unabated. HRV indexes activity in the vagus nerve, the primary nerve in the parasympathetic nervous system. Given its critical role in both mental and physical health, it is perhaps the most important nerve in the human body. The association between psychiatric disorders-particularly the mood and anxiety disorders-and HRV has attracted much research attention. Debate has focused in particular on whether HRV is reduced in the mood and anxiety disorders or whether HRV reductions are driven primarily by medications for these conditions. Drawing definitive conclusions on the basis of the reported evidence has been made difficult by a variety of methodological factors, which need to be considered in future research. Researchers also need to give consideration to what might moderate HRV reductions in order to better clarify conditions under which effects may or may not be observed.