Syncope, defined as a transient loss of consciousness and postural tone with spontaneous recovery and no neurologic sequelae, is among one of the most common causes of consultation with a physician. The diagnostic workup is complex but can be simplified if focused on the underlying condition. Prognosis is highly dependent on the presence or absence of structural heart disease, primarily the presence of cardiomyopathy regardless of etiology, particularly if the left ventricular (LV) function is less than 35%. The diagnostic approach to the patient with recurrent syncope and no structural heart disease is targeted to rule out neurally mediated causes. This approach usually includes a tilt table test (ie, head-up tilt), carotid sinus massage in patients older than 55 years, and an adenosine challenge test in patients who remain with unexplained syncope. Unexplained syncope in patients with reduced LV function (< 35%) may be potentially life-threatening. Infrequent causes of syncope should be sought in younger patients with a family history of sudden cardiac death. Channelopathies such as the long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia are among this variety. Therapy should address the potential mechanism of syncope. In neurally mediated causes, restoration of orthostatic tolerance, primarily by increasing volume during orthostatic stress, is recommended. Physiologic countermaneuvers and increase in salt and water intake are usually the initial therapy. With syncope in patients with an LV dysfunction (< 35%), an ICD is frequently recommended after ruling out common causes of syncope. Syncope in the elderly is usually multifactorial and therapy should include reassessment of multiple medications, which can promote neurally mediated syncope as well as searching for bradycardic causes. Empiric pacing may be used in this complex group of patients.