Cardiac resynchronization therapy (CRT) is a well-accepted and effective therapy for treating patients with a wide QRS complex, significant left ventricular systolic dysfunction, and symptoms of advanced heart failure. However, approximately 25% to 30% of patients fail to respond to this therapy. Most large studies have used electrical dyssynchrony (wide QRS) as a main entrance criterion. Emerging data suggest that mechanical dyssynchrony may be a more important factor in selecting appropriate candidates for CRT. New echocardiographic (ECHO) imaging modalities such as tissue Doppler imaging, three-dimensional ECHO, and speckle tracking ECHO are able to quantify left ventricular mechanical dyssynchrony. These techniques are currently being used to assist in the selection of patients for CRT. Recently published and ongoing studies are addressing the use of CRT in patients who do not meet the standard criteria, such as patients with atrial fibrillation, mild to moderate heart failure, narrow QRS complex, and acute myocardial infarction.