Cardiovascular defects (CVD) are an important feature in children with DiGeorge/velo-cardio-facial/conotruncal anomaly face syndrome (DGS/VCFS/CTAF) associated with a chromosome 22q11 deletion (del 22q11). This chapter describes the cardiac anatomy of CVD associated with VCFS and its diagnostic and surgical implications. Children with CVD and VCFS usually have laevocardia, viscero-atrial situs solitus with d-loop of the ventricle, and atrioventricular concordance. There is limited information available on the natural history and the clinical course of children with CVD and VCFS. Prenatal diagnosis of this association, by means of fetal echocardiography and amniocentesis is possible nowadays. Advances in pediatric cardiac surgery have made it possible to treat the majority of patients with CVD with a very low operative risk and excellent long-term outlook. Before cardiac surgery, all children with cardiac defects and VCFS need an accurate clinical investigation to exclude the presence of additional, extracardiac anomalies.