This review clearly indicates that a clinical picture of pure, isolated mitral insufficiency constitutes an interesting diagnostic challenge. In adult patients especially, this common valvular lesion is often nonrheumatic and may be found in a variety of cardiac conditions. The following provides a general orientation for their differential diagnosis. The first clue to the presence of papillary muscle dysfunction, a "spontaneous" chordal rupture, or a congenital or traumatic lesion which may account for the mitral insufficiency, may be derived from the patient's case history. A history suggesting systemic manifestations raises the possibility of atrial myxoma. When a familial incidence is reported, various syndromes or a cardiomyopathy should be considered as the etiology of the mitral incompetence. The auscultatory findings are typical in the mid-late systolic click and murmur syndrome, but recognition of this condition may require careful examination of the patient in different postures. The possibility of obstructive cardiomyopathy may be confirmed by the characteristic carotid pressure tracing. ECG findings of acute or chronic coronary heart disease favor the possibility of papillary muscle dysfunction. In addition, the ECG may support the clinical impression of a cardiomyopathy. Fluoroscopy may show calcification of the coronary arteries and/or dyskinetic left ventricular contractions in papillary muscle dysfunction, intracardiac calcifications in atrial space-occupying lesions, or calcification of a mitral annulus. Chest X-rays may contribute to the diagnosis of acute mitral insufficiency by showing a relatively small left atrium and ventricle in the presence of severe congestive failure. While echocardiography is invaluable as a noninvasive procedure and readily demonstrates the presence of a flail mitral leaflet from chordal rupture, or aids in the recognition of obstructive cardiomyopathy, an atrial space-occupying lesion, or of a billowing mitral leaflet, left ventriculography and coronary angiography constitute the procedure of choice for the fine anatomic diagnosis and functional evaluation of most cases. The accurate diagnosis of the anatomic disruption of the mitral valvular apparatus, as well as of the state of the myocardium and of the coronary arteries, is of particular importance in symptomatic patients, in order to determine the prognosis and to plan the surgical approach.