The long QT syndrome is one of the most prevalent and studied among the inherited arrhythmogenic conditions that expose individuals to a high risk of sudden death, from early infancy throughout the entire lifespan. The hallmark of the syndrome is its heterogeneity in genetic background, phenotypic manifestations, responses to therapy, and prognosis. ß-Blockers are successful in protecting most patients from adverse events, but some remain vulnerable despite antiadrenergic drugs, and require more aggressive therapeutic approaches. Effective stratification based on clinical and genetic parameters is crucial to identify patients with the highest risk and to avoid overtreatment.