Initial studies established patient selection criteria for cardiac resynchronization therapy (CRT) as left ventricular ejection fraction less than or equal to 35%, QRS greater than or equal to 120 ms, and New York Heart Association 3–4. Based on newer data, post hoc analyses, and meta-analyses, these criteria have been refined and guidelines updated, highlighting left bundle branch morphology and QRS greater than 150 ms in selecting patients with a likelihood of favorable outcomes. Guidelines will change as more data become available; the decision to apply CRT should be based on patient clinical profile and the balance of risk tolerance and likelihood of benefit.