We review the use of real-time three-dimensional transesophageal echocardiography (RT3D-TEE) in guiding percutaneous catheter-based procedures to repair structural heart defects. The utility of this novel imaging technique in percutaneous mitral valve repair and valvuloplasty, aortic valve insertion, device closure of atrial and ventricular septal defects, obliteration of the left atrial appendage, and pulmonary vein ablation is described. The main advantages of RT3D-TEE lie in its ability to visualize the entire length of intracardiac devices, including their tips, and to demonstrate their relationship to cardiac structures, to provide en face views of cardiac structures (such as the interatrial septum and the mitral valve) that are unobtainable in real time by any other imaging technique, and to allow for continuous monitoring during the procedure. It is likely that RT3D-TEE will become the standard of care for guidance of percutaneous, catheter-based procedures.