The hereditary Long QT syndrome (LQTS) is a genetic channelopathy with variable penetrance that is associated with increased propensity for polymorphic ventricular tachyarrhythmias and sudden cardiac death in young individuals with normal cardiac morphology. The diagnosis of this genetic disorder relies on a constellation of electrocardiographic, clinical, and genetic factors. Accumulating data from recent studies indicate that the clinical course of affected LQTS patients is time-dependent and age-specific, demonstrating important gender differences among age groups. Risk assessment should consider age-gender interactions, prior syncopal history, QT-interval duration, and genetic factors. Beta-blockers constitute the mainstay therapy for LQTS, while left cardiac sympathetic denervation and implantation of a cardioverter defibrillator should be considered in patients who remain symptomatic despite beta-blocker therapy. Current and ongoing studies are also evaluating genotype-specific therapies that may reduce the risk for life-threatening cardiac events in high-risk LQTS patients.