Endomyocardial biopsy (EMB) is widely used for surveillance of cardiac allograft rejection and for the diagnosis of unexplained ventricular dysfunction. Typically, EMB is performed through the jugular or femoral veins and is associated with a serious acute complication rate of less than 1% using current flexible bioptomes. Although it is accepted that EMB should be used to monitor for rejection after transplant, use of EMB for the diagnosis of various myocardial diseases is controversial. Diagnosis of myocardial disease in the nontransplant recipient is often successful via noninvasive investigations including laboratory evaluation; echocardiography, nuclear studies, and magnetic resonance imaging can yield specific diagnoses in the absence of invasive EMB. Therefore, use of the technique is patient specific and depends on the potential prognostic and treatment information gained by establishing a pathologic diagnosis beyond noninvasive testing.