Despite progress in the management of heart failure (HF) using pharmacotherapy, the mortality and morbidity associated with this condition remain unacceptably high. Cardiac resynchronization therapy (CRT), a left-sided pacing therapy for drug-refractory and highly symptomatic HF patients with ventricular conduction delay, has been shown to improve left ventricular (LV) systolic function, myocardial oxygen consumption, and New York Heart Association functional class and to inhibit or reverse LV chamber dilation and remodeling. Atrial fibrillation is common in patients with HF and is associated with significant worsening of HF and myocardial function. Only recently have trials been designed to specifically study CRT in patients with HF and chronic atrial fibrillation. These studies have shown that CRT with biventricular or univentricular LV pacing in patients with atrial fibrillation corrects mechanical dyssynchrony and results in significant and sustained improvement in functional capacity, LV ejection fraction, quality of life, and QRS duration.