Patients commonly present with syncope at emergency departments and other facilities for urgent care. Syncope is understood by physicians to be a transient, self-terminating period of cerebral hypoperfusion that usually results from systemic hypotension, and clinical guidelines for the care of patients with presumed syncope are available. However, the diagnosis and management of such patients continue to pose important diagnostic, therapeutic, and economic challenges, which are the focus of this Review. First, we discuss how to improve symptom characterization to distinguish syncope from other forms of transient loss of consciousness and syncope mimics. Second, we compare methods of risk stratification in patients with suspected syncope, and recommend the introduction of syncope clinics with enhanced interdisciplinary collaboration to optimize patient care at reduced expense. Third, we highlight the importance of the appropriate selection of diagnostic tools and treatment strategies in these syncope clinics. Finally, we address the difficulties associated with therapy for the most-common form of syncopeg-vasovagal or reflex syncope.