The criteria for scientific validation of the entities currently subsumed under the DSM-IV category of "Psychological Factors Affecting a Medical Condition" have never been clearly enumerated. Historically, its precursor category ("Psychophysiological Disorder") was rarely used, and predicated upon clinical observation of personality styles among patients with specific physical illnesses, or clinical observations relating psychosocial events and symptom exacerbation. Because of logical flaws with either of these methods, clarification of the most rigorous criteria for demonstrating a cause-effect relationship is necessary. With the increase in well-designed and carefully executed epidemiological and treatment studies, this diagnostic category has evolved into an arena where cutting-edge insights and therapies are becoming available for a growing variety of medical conditions, especially ischemic coronary heart disease. The present article reviews the nature of the scientific evidence necessary to accept an etiological or aggravating role for psychological events.