Cardiac resynchronization therapy (CRT) is a proven treatment adjunct for selected patients with heart failure and evidence of ventricular dyssynchrony. When applying most contemporary guidelines the accepted response rate has remained static with up to one-third of patients failing to respond. Empiric lateral/posterolateral lead positioning may not be the optimal strategy in all patients, particularly in those with extensive scar and there have been developments that suggest an approach whereby the latest mechanically activating segment is targeted for left ventricular (LV) lead placement may be of some benefit. Additionally, alternative means of delivering CRT, either by means of multi-site pacing or LV endocardial pacing, have similarly shown promise. At a time where novel predictors of response to CRT have proved disappointing in multi-center trials, a paradigm shift away from prediction towards better delivery of CRT may potentially be of most benefit to the significant minority who do not respond.