Syncope is defined as transient loss of consciousness as a result of inadequate cerebral perfusion. The causes of syncope fall into five broad categories: neurally mediated, orthostatic (the most frequent causes), cardiac arrhythmias, structural cardiovascular (relatively uncommon cause), and cerebrovascular (very rare). The initial evaluation of the syncope patient includes a detailed medical history and physical exam, and usually an ECG and echocardiogram. Thereafter, selected additional testing (e.g. ambulatory ECG recording, autonomic function testing, electrophysiologic study) may be needed on a case-by-case basis. Neurally mediated and orthostatic syncope should first be treated by conservative therapies including hydration/volume expanders and physical counter-maneuvers. Various drugs may play a role as second-line of treatment. However, apart from midodrine, randomized studies of drug therapy are largely lacking, and most agents have not proved to be predictably effective. For syncope due to cardiac arrhythmias, treatment options (depending on the specific circumstance) include ablation of the arrhythmia origin, antiarrhythmic drugs, and/or implantable devices (pacemakers and defibrillators). In the case of syncope due to structural cardiovascular defects (e.g. acute myocardial ischemia, pulmonary hypertension, obstructive cardiomyopathy), treatment is aimed at ameliorating the underlying structural defect. In brief, establishing a specific cause(s) for syncope is crucial. Only then can a potentially effective treatment strategy be contemplated.