The cause of CDH remains largely unknown. Although teratogenic factors have been described, no single gene mutation can be held responsible for this major congenital anomaly. The genetic background of familiar occurrence is variable. Careful documentation of both isolated and familiar cases, and the application of new techniques such as fluorescent in situ hybridization (FISH) and differential display in selected cases, might result in new explanations for possible genetic inheritance. Clinical evaluation of associated anomalies, together with increasing awareness of the genes involved in lung development, especially those guiding mesenchymal growth, will have great impact on increasing knowledge of the cause of this devastating anomaly.