The congenital long-QT syndrome (LQTS) is a life-threatening cardiac arrhythmia syndrome that represents a leading cause of sudden death in the young. LQTS is typically characterized by a prolongation of the QT interval on the ECG and by the occurrence of syncope or cardiac arrest, mainly precipitated by emotional or physical stress. Since 1975,1 2 hereditary variants, the Romano-Ward (RW) syndrome2,3 and the extremely severe Jervell and Lange-Nielsen (JLN) syndrome,4,5 which is associated with congenital deafness, have been included under the comprehensive name of LQTS, one of the best understood monogenic diseases. The usual mode of inheritance for RW is autosomal dominant, whereas JLN shows autosomal recessive inheritance or sporadic cases of compound heterozygosity. Several reasons make LQTS an important disease. It can often be a lethal disorder, and symptomatic patients left without therapy have a high mortality rate, 21% within 1 year from the first syncope.6 However, with proper treatment, mortality is now ≈1% during a 15-year follow-up.7 This makes inexcusable the existence of symptomatic but undiagnosed patients. LQTS is without doubt the cardiac disease in which molecular biology and genetics have made the greatest progress and unquestionably is the best example of genotype-phenotype correlation. In this regard, it represents a paradigm for sudden cardiac death, and its progressive unraveling helps to better understand the mechanisms underlying sudden death in more complex disorders, such as ischemic heart disease and heart failure. This review will outline the current knowledge about the genetics of LQTS and provide essential clinical data, whereas its primary focus will be on our approach to the clinical management of these patients. The electrocardiographic QT interval represents the depolarization and the repolarization phases of the cardiac action potential. The interplay of several ion channels determines the action potential …