The prenatal detection of structural cardiac malformations has greatly benefited from the advances in echo Doppler technology and the in-depth training of specialists in this area. This opens up new possibilities, now and in the future, for developing in utero therapies. It also allows a better knowledge of the underlying mechanisms and developmental timing that lead to structural congenital heart disease (CHD), based on a marked progress involving genetic and epigenetic causes. Gene mutations are discovered in the fetus and parents, and pathways can be unraveled using mouse transgene technology. Epigenetic causes are also receiving attention, but have thus far been underestimated as approximately 85% of CHD is determined to have a multifactorial background that combines a genetic susceptibility with epigenetic influences. Studies in animal models, including chicken, quail, zebrafish, and even more primitive Chordates, contribute relevant data. In essence, cardiac development shows basic similarities of the major processes involved between species. Therefore mechanisms unraveled in animal models can be reliably used in understanding normal human cardiac development and CHD .