Sophisticated studies of the pathophysiology of chest pain in patients without serious heart disease began with Likoff's report of 15 women with recurrent chest pain, abnormal electrocardiograms (ECGs), and normal coronary angiograms. The most promising current hypothesis on the mechanism of chest pain syndromes postulates that the essential common feature in these patients is abnormal visceral pain perception. Research into the factors which contribute to chest pain syndromes has led to the development of at least four major hypotheses: esophageal spasm, esophageal irritation, smooth muscle dysfunction, and microvascular angina. An understanding of the history and the current pathogenetic mechanisms of chest pain syndromes provides a roadmap for efficiently evaluating chest pain patients. A systematic approach to each of the factors contributing to the patient's recurrent chest pain is best coordinated by a primary care physician over the course of the syndrome.