Cardiac resynchronization therapy (CRT) is the therapy of choice for patients with symptomatic systolic heart failure (HF) and left bundle branch block (LBBB), despite optimal medical therapy (OMT). The recently published 2021 European Society of Cardiology (ESC) Guidelines on cardiac pacing and cardiac resynchronization therapy highlight the importance of CRT on top of OMT in HF patients with left ventricular ejection fraction (LVEF) ≤ 35%, sinus rhythm and typical LBBB with QRS duration ≥ 150 ms. In the presence of medically intractable or recurrent after catheter ablation atrial fibrillation (AF), AV nodal ablation as an adjuvant therapy becomes more relevant in patients qualifying for the implantation of a biventricular system. Furthermore, CRT may be considered in cases when increased pacing of the right ventricle is not desirable. However, alternative pacing sites and strategies are currently available, if the CRT is not feasible and effective in patients. However, strategies targeting "multi-sides" or using "multi-leads" have shown superiority over classic CRT. On the other hand, conduction system pacing seems to be a promising technique. Although early results are positive, consistency during the long term is pending. The indication for additional defibrillation therapy (ICD) may occasionally be unnecessary and has to be considered individually. Due to the great development and success of heart failure drug therapy, its positive effect on LV function can lead to enormous improvement. Physicians must await these effects and findings, which hopefully could lead to a relevant LV improvement resulting in a definitive decision against an ICD.