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In the early 1990s, attempts at treating patients with dilated cardiomyopathy and end-stage heart failure by using right-sided, dual-chamber pacing met with equivocal results. Although initially discouraging, this work did provide further insight into the electromechanical consequences of advanced heart failure and suggested that atrial-synchronized biventricular pacing, or cardiac resynchronization therapy, might provide better and more consistent symptomatic and hemodynamic improvement. Several studies have recently validated the safety and efficacy of cardiac resynchronization therapy in advanced heart failure. Data from these studies have shown statistically significant improvements in left ventricular ejection fraction, New York Heart Association class, exercise tolerance, and quality of life. Observed reductions in morbidity and mortality await confirmation from ongoing large-scale outcomes studies. This article reviews the evolution of pacing in heart failure and discusses the underlying mechanisms that are potentially responsible for the improvement seen in patients receiving cardiac resynchronization therapy. In addition, the results of recently completed clinical trials, as well as the status of ongoing clinical trials, are reviewed.