A strong body of evidence exists to support cardiac resynchronization therapy (CRT) as a mainstay in the management of advanced heart failure for patients with LBBB-type QRS prolongation. Progress in technology has made percutaneous CRT easier to achieve. Skillful operators can readily reach implantation success rates in excess of 95%. Nevertheless, not every patient selected for CRT, according to current criteria, benefits from this therapy. Several factors contribute to the lack of benefit in these patients, including inadequate patient selection, lack of control of atrial arrhythmias, procedural factors and suboptimal pacemaker settings. It remains to be seen whether newer technology and pacing algorithms will increase response rates to CRT. The focus of this review will be to examine which patients benefit most from CRT and to assess methods for optimizing patient selection in order to achieve maximum benefit from this pivotal therapy.