Many patients with left ventricular systolic dysfunction may benefit from cardiac resynchronization therapy; however, approximately 30% of patients do not experience significant clinical improvement with this treatment. AV and VV delay optimization techniques have included echocardiography, device-based algorithms, and several other novel noninvasive techniques. Using these techniques to optimize device settings has been shown to improve hemodynamic function acutely; however, the long-term clinical benefit is limited. In most cases, an empiric AV delay with simultaneous biventricular or left ventricular pacing is adequate. The value of optimization of these intervals in “nonresponders” still requires further investigation.