The role of invasive mapping in the context of cardiac resynchronization has been essentially confined to improving knowledge of the depolarization processes and spread of ventricular activation. Experimental and limited clinical data obtained from high resolution three-dimensional contact and non-contact mapping have consistently pointed to the heterogeneity and the complexity of ventricular sequential activation in heart failure with conduction disturbance. The present article reviews current knowledge about activation mapping in patients with different types of ventricular conduction disturbance (right and left bundle branch block) putting this in the perspective of selection of most appropriate pacing site in cardiac resynchronization therapy (CRT) patients. Furthermore, recent comparative data of epicardial and endocardial pacing have been discussed. There is little doubt that invasive mapping will continue to contribute in a substantial manner to progresses in CRT especially in the new era of endocardial pacing. Therefore, it is possible to envision that endocardial mapping may serve to selectively target the most adequate positions for the left ventricular lead in order to optimize CRT.