In 1993, the cardiac surgeon Bakker et al. [1] introduced biventricular pacing as a novel method to treat heart failure by synchronous stimulation of the right and left ventricle. After this first-in-man implantation, the rapid development of transvenous left ventricular (LV) leads and the implementation of biventricular pacing in implantable cardioverter/defibrillators have established cardiac resynchronisation therapy (CRT) as a standard treatment of heart failure with systolic LV dysfunction and broad QRS complexes. Although the milestone trials have proven the benefit of CRT (reduction in mortality and morbidity, reverse remodelling, improvement of LV function), the prediction of CRT response still remains a challenge [2–6]. Because of the high number of CRT non-responders, especially in patients with unspecific widening of the QRS complex, class I indication for CRT was restricted to heart failure patients with typical left bundle branch block (LBBB) in the European Heart Rhythm Association guidelines update of 2013. Two-dimensional echocardiography is the most widely used noninvasive method for the evaluation of LV function and assessment of reverse remodelling after CRT; however it has as yet failed to play an additional role in determining the indication for CRT [7]. Furthermore, even though mechanical dyssynchrony was thought to be present using echocardiographic parameters, CRT was harmful in those patients with narrow QRS complexes [8]. In more than 20 years of experience with CRT-related issues, we have deepened our knowledge about indication, implantation, evaluation, and optimisation of CRT. With the rapid development of the CRT technology new challenges arise.