Sex medicine can be applied to define the effect of male or female sex-associated differences on the prevalence of congenital heart defects (CHDs), on clinical manifestation of the latter, on means of dealing with the defects and facing consequent surgical treatment, as well as on the success of surgery. The widespread use of modern databases has undoubtedly enhanced the possibility of these observations compared to the past, when findings were limited to case series from single cardiology or paediatric heart surgery units. The aim of the present review is to assess all publications present in the literature on sex differences and CHD, placing particular emphasis on both contradictory aspects and less acknowledged issues. Furthermore, a section of the review is devoted to the effect of sex differences on cardiac arrhythmias, particularly the largely genetically predetermined electrophysiological differences observed between men and women.