Exploration into the underlying genetic causes of congenital long QT syndrome (LQTS) has opened the door to our understanding of repolarization disorders. Expression of LQTS mutations has led to an improved understanding of the mechanisms of arrhythmogenesis, clinical diagnostic tools and channel specific therapy. Further insight into the mechanisms underlying the more common acquired LQTS is emerging from gene and channel studies that have used the congenital syndrome as a springboard for directing research to improve understanding. This review summarizes the clinical, genetic and electrophysiological understanding of congenital and acquired LQTS.