Nonresponse to cardiac resynchronization therapy (CRT) is still a major issue in therapy expansion. The description of fast, simple, cost-effective methods to optimize CRT could help in adapting pacing intervals to individual patients. A better understanding of the importance of appropriate patient selection, left ventricular lead placement, and device programming, together with a multidisciplinary approach and an optimal follow-up of the patients, may reduce the percentage of nonresponders.