Numerous randomized clinical trials demonstrated the beneficial effects of cardiac resynchronization therapy (CRT) in the treatment of moderate to severe heart failure. Despite careful patient selection, there is still a percentage of non-responders, that is as high as 30-50%. Patients are selected mainly on electrocardiogram criteria. Recent studies have observed that the severity of mechanical systolic asynchrony is a much better predictor of a response after CRT. Echocardiography allows a non-invasive evaluation atrioventricular and inter- and intraventricular synchrony; furthermore, recent advances have provided direct evidence of wall motion resynchronization in patients receiving CRT. Nevertheless, although many authors tried to search for the best echocardiographic index to identify systolic asynchrony, and consequently responders to CRT before the procedure, this issue is still a matter of debate. Our aim was to make an updated review of the more recent studies on this topic.