Cardiac resynchronization therapy (CRT) is an established treatment for selected heart failure patients with conduction disease. Many studies aimed at quantifying mechanical dyssynchrony in CRT candidates when it became apparent that 30-50% of CRT recipients showed no improvement after implantation. As these, often echocardiography-based, measurements have not yet succeeded in estimating the mechanical substrate in an accurate and reproducible manner, interest in electrical substrate has renewed. In this review, current knowledge concerning electrical substrate in CRT candidates will be explored and applied to current CRT practice, highlighting why the electrical substrate is both essential and sufficient for successful CRT. Finally, novel ways to better measure and treat the electrical substrate are discussed.