Ventricular dysfunction and ventricular dilatation (a hallmark of heart failure) may cause atrial and ventricular conduction delays. Pharmacological treatment is unable to correct such conduction delays and their associated detrimental mechanical effects. In contrast, cardiac resynchronization therapy (CRT) has successfully been used in patients with heart failure to correct electrical activation abnormalities, resulting in major improvements in haemodynamic and cardiac pumping efficiency. Data collected by independent investigators during acute testing consistently show that CRT increases stroke volume, improves ventricular contractility, and reduces diastolic and systolic mitral insufficiency. In patients with heart failure chronically paced with resynchronization devices, small randomized trials have consistently reported short-term and mid-term improvements in functional class, exercise capacity and quality of life. Significant symptomatic benefits have also been confirmed in a large European registry, including over 1000 patients followed for 6 months after implantation of a CRT device. Furthermore, a resetting of the neurohumoral status has been documented in patients receiving CRT. Two completed studies have reported fewer hospitalizations with CRT than with pharmacological therapy. Trials examining the effects of CRT on long-term morbidity and mortality are in progress.