Recurrent chest pain in the presence of normal coronary arteries is a common and perplexing problem in primary care medicine and cardiology and is associated with significant morbidity and health care utilization. A series of carefully controlled prospective studies conducted over the past decade have suggested a strong association between this syndrome and the presence of anxiety disorders. Thirty percent to 50% of patients with recurrent chest pain and normal coronary arteries meet criteria for panic disorder. Generalized anxiety disorder may also be associated with this syndrome. In contrast, major depression seems strongly associated with the syndrome only when it presents as a comorbidity with panic disorder. Reluctance of nonpsychiatric physicians to diagnose and treat anxiety disorders in this population may reflect a lack of knowledge of the well-established pathophysiologic mechanisms that can mediate the association of anxiety disorders and cardiac symptoms. We propose a conceptual framework, derived from the neurologic literature and from recent studies using positron emission tomography and intravenous procaine challenge, which links anxiety and subjective cardiovascular symptoms to abnormal activity in neural circuits involving the anterior limbic system of the brain. This neuropsychiatric model of the role of anxiety disorders in the pathophysiology of chest pain in patients with normal coronary arteries is proposed to strengthen the rationale for the identification and treatment of anxiety disorders in this population by nonpsychiatric physicians.