Cardiac resynchronization therapy (CRT) represents a new class of heart failure therapy that provides symptom relief and decreased need of hospitalization in a significant number of patients already receiving maximal medical intervention. Patients with ischemic or nonischemic dilated cardiomyopathy, coupled with interventricular conduction delays, who have New York Heart Association class III or IV symptoms, are currently candidates for CRT. This device-based intervention reverses adverse ventricular remodeling, decreases the severity of mitral regurgitation, and increases cardiac efficiency and output. New selection criteria are being considered in an attempt to identify patients who have a high chance of responding, and possibly, to identify patients that have a high chance of not responding to CRT. These efforts are in response to the 20% to 25% "nonresponder" rate observed when the currently accepted inclusion criteria are used. Other patient populations may also benefit from CRT, including those in need of antibradycardia pacing, patients with atrial fibrillation, and some who meet the criteria for prophylactic implantation of a cardiac defibrillator. This review focuses on the current strategies to refine patient selection criteria and addresses some of the practical issues in prescribing CRT.