The analysis of heart rate variability (HRV) is becoming widely used in clinical research to provide a window into autonomic control of HR. This technique has been valuable in elucidating the autonomic underpinnings of panic disorder (PD), a condition that is marked by reports of heart palpitations. A body of research has emerged that implicates a relative reduction in HRV and cardiac vagal tone in PD, as indicated by various HRV measures. These data are consistent with the cardiac symptoms of panic attacks, as well as with developmental evidence that links high vagal tone with enhanced attention, effective emotion regulation, and organismic responsivity. Implications of these findings for nosology and pathophysiology are discussed. Reports of reduced HRV in PD contrast with portrayals of excess autonomic lability in anxiety. This contradiction is addressed in the context of traditional homeostatic models versus a systems perspective that views physiologic variability as essential to overall stability.