Panic is a psychologic symptom with prominent physiologic manifestations. Pathophysiologic theories need to explain both the central emotional state and peripheral symptoms. This paper reviews current findings and hypotheses from studies using two strategies for understanding panic. First, recent results from provocative tests using sodium lactate, caffeine, CO2, yohimbine, and isoproterenol suggest panic patients have a special sensitivity to these substances. Underlying mechanisms may be related to abnormal functioning of the central noradrenergic (locus ceruleus) system. However, cognitive and behavioral aspects of pharmacologic provocative testing need further study. Second, naturalistic studies support findings of peripheral physiologic activation during panic, but do not show evidence for sustained hyperactivity throughout the day. Studies of phobic patients demonstrate the potential for imagined fear to provoke physiologic changes, again underlining the need to pay attention to psychologic aspects of panic.