Cardiac disease and thrombosis are intimately related in adults, but primary myocardial infarction in children is rare. Homozygous familial hyperlipidemia occurs in approximately 1 million children, and causes severe coronary artery disease during childhood. Kawasaki's disease is an acquired inflammatory disorder, which, if untreated, leads to coronary artery aneurysms and subsequent myocardial infarction. The current understanding of the pathophysiology and management of these conditions is discussed. More commonly, the relationship between cardiac disease in children and thrombosis is that children being treated for congenital structural cardiac disease develop iatrogenic thrombosis, most commonly precipitated by central venous access. The epidemiology of common treatment-induced thrombosis is described, and management guidelines presented. Finally, many cardiac surgical procedures increase the risk of thrombosis, and prophylactic antithrombotic therapy is commonly used. The current evidence for prophylaxis in different clinical situations is presented. Additional study is required in all areas to improve the outcome for children affected by cardiac disease and thrombosis.