Although cardiac resynchronization therapy improves morbidity and mortality in patients with cardiomyopathy, heart failure, and electrical dyssynchrony, the rate of nonresponders using standard indications and implant techniques is still high. Optimal coronary sinus lead positioning is important to increase the chance of successful resynchronization. Patient factors such as cause of heart failure, type of dyssynchrony, scar burden, coronary sinus anatomy, and phrenic nerve capture may affect the efficacy of the therapy. Several modalities are under investigation. Alternative left ventricular lead implantation strategies are occasionally required when the transvenous route is not feasible or would result in a suboptimal lead position.