Down syndrome (DS), as a typical genomic aneuploidy, is a common cause of various birth defects, among which is congenital heart disease (CHD).40-60% neonates with DS have some kinds of CHD. However, the molecular pathogenic mechanisms of DS associated CHD are still not fully understood. This review summarizes available studies on DS associated CHD from seven aspects so as to provide a crucial and updated overview of what we known so far in this domain.