In this issue of the Journal, Giraldi et al. (1) compare transvenous and epicardial lead placement in patients with unfavorable coronary sinus anatomy. Patients who met standard criteria for cardiac resynchronization therapy (CRT) including left ventricular (LV) dysfunction, New York Heart Association class III to IV congestive heart failure, and left bundle branch block, who were on optimal medical therapy underwent pre-operative multislice computed tomography to evaluate coronary sinus (CS) anatomy. Patients with CS veins that were absent, tortuous, angled acutely, or very small were prospectively randomized to LV lead implantation by epicardial minimally invasive thoracotomy versus conventional endocardial lead placement. Whereas the surgically positioned leads were placed over the mid-basal segments of the posterolateral LV wall, the transvenously positioned leads could not be placed in these segments because of suboptimal CS anatomy. At 1 year, the surgical patients, but not the patients implanted transvenously, had significant improvements in New York Heart Association functional class, LV ejection fraction, LV end-systolic volume, and peak Vo2/kg.