Cardiac resynchronization therapy (CRT) is an established therapeutic option in symptomatic heart failure with reduced ejection fraction and evidence of left ventricular (LV) conduction delay (QRS width ≥120 ms), especially when typical left bundle branch block is present. The rationale behind CRT is restoration of aberrant LV electrical activation. As there is considerable heterogeneity of the LV electrical activation pattern among CRT candidates, an individualized approach with targeting of the LV lead in the region of latest electrical activation while avoiding scar tissue may enhance CRT response. Echocardiography, electro anatomic mapping, and cardiac magnetic resonance imaging with late gadolinium enhancement are helpful to guide such targeted LV lead placement. However, an important limitation remains the anatomy of the coronary sinus, which often does not allow concordant LV lead placement in the optimal region. Epicardial LV lead placement through minimal invasive surgery or endocardial LV lead placement through transseptal punction may overcome this limitation, obviously with an increased complication risk. Furthermore, recent pacing algorithms suggest superiority of LV-only versus biventricular pacing in patients with preserved atrio ventricular (AV) conduction and a typical LBBB pattern. Finally, pacing from only one LV site might not overcome the wide electrical dispersion often seen in patients with LV conduction delays. Therefore, multisite pacing has gained significant interest to improve CRT response. The use of multiple LV leads may potentially lead to more favorable reverse remodeling, improved functional capacity and quality of life in CRT candidates, but adverse events and a shorter battery span are more frequent because of the extra lead. The use of one multipolar LV lead increases the number of pacing configurations within the same coronary sinus side branch (within small distances from each other) without the use of an additional lead. Small observational studies suggest that more effective resynchronization can be achieved with this approach. Finally, there are many reasons for non effective CRT delivery in carefully selected patients with an adequately implanted device. Multidisciplinary, post implantation care inside a dedicated CRT clinic ensures optimal CRT delivery, improves response rate and should be considered standard of care.