Extraordinary diagnostic precision and definitive therapies characterize the current management of congenital heart disease, but the state of the art is not perfect; and in spite of tremendous progress in diagnosis and treatment, our understanding of cause is rudimentary. During the past decade, advances in molecular genetics have defined disease gene loci and lead to identification of genes whose mutations cause congenital heart disease. Identification of additional genes and mutations will lead to improved understanding of pathophysiology of cardiovascular disease in the young. Better understanding of pathophysiology and identification of individuals at risk will provide an opportunity to develop preventive strategies. Taken as a whole, the prospect of understanding the genetic basis of congenital heart disease and translating it into improved diagnostic and therapeutic strategies has never been better.