Right ventricular pacing at various sites and shortened atrioventricular (AV) delay has failed to demonstrate a convincing short-term and long-term improvement of left ventricular function. Left-ventricular-based stimulation offers a new therapeutic option for patients with symptomatic congestive heart failure and conduction disturbances, especially of left bundle-branch block configuration. Left ventricular mechanical improvement seems mainly dependent on the pacing site, in addition to optimizing the AV delay. Predominantly retrospective data suggest that pacing the posterolateral free wall results in the greatest hemodynamic improvement. Based on the evaluation of different pacing sites in 2 patients, we noted that site is of major importance for maximal improvement of left ventricular function, and pacing at a suboptimal site can even deteriorate left ventricular contractility. Moreover, lead technology has advanced rapidly and different areas of the left ventricle can now be reached transvenously for acute and chronic placement. Therefore, ongoing trials will help to identify the optimal pacing site and might indicate whether invasive testing will be required in the future.