One of the most frustrating challenges faced by the forensic pathologist is the inability to determine the cause of death in a young person previously thought healthy. The four steps in the investigation of a sudden death include obtaining the history and scene information, performing a gross and microscopic autopsy, performing appropriate laboratory tests, and making the diagnosis. When examining the heart grossly it is important to preserve the anatomic landmarks, section the coronary arteries closely, and recognize lethal abnormalities such as anomalous origin of the coronary arteries. Specimens useful for toxicologic analysis include whole blood, serum, vitreous humor, gastric contents, bile, urine a purple top tube of blood, and frozen myocardium and spleen. Lethal cardiac diseases with minimal or no anatomic findings include Brugada and Garg's syndromes, the long QT syndrome, and Wolff-Parkinson-White (WPW) syndrome. Consultation with other experts, including cardiac pathologists, cardiologists, electrophysiologists, and molecular biologists, may be helpful in determining a cause of death.