There are important male-female differences in human cardiac rhythm and arrhythmias. For example, women have faster basal heart rates and longer QT intervals than men. These differences relate not only to gender but to gonadal steroids. For example, drugs that prolong repolarization induce torsades de pointes more frequently in women than men; female gender is an independent risk factor for syncope and sudden death in the congenital long QT syndrome; and the higher propensity toward arrhythmia in normal females is associated with fundamental male-female differences in repolarization. Many of these male-female differences appear related to the molecular determinants of the ion channels that control cardiac impulse initiation and repolarization. Studies performed in human subjects and, especially, in animal models have demonstrated a number of differences among ion channel properties, most importantly, in repolarizing potassium currents that appear to be responsible for many of the basal repolarization differences. Beyond this, and impacting particularly on drug-induced arrhythmias, both the presence and the metabolism of gonadal steroids can modify the metabolism of a variety of drugs, resulting in elevated plasma levels and accentuated actions. Another important variable is age, with male-female differences being most prominent when gonadal steroid activity is greatest, and being of lesser importance in earlier and later years. The variety of male-female differences in cardiac rhythm and the mechanisms determining the differences in repolarization and arrhythmias in males and females will be discussed.