Cardiac resynchronization therapy is demonstrated to be effective in patients with advanced heart failure. Correcting mechanical dyssynchrony is proposed as the predominant mechanism of response. Achieving optimum left ventricular lead position, at the site of maximal mechanical dyssynchrony but away from transmural scar, is identified as one of the main determinants of both symptomatic and prognostic benefit. Strategies employing multimodality cardiac imaging techniques have been used to identify this optimal pacing site, in addition to any potential anatomical limitations to successful implantation. Speckle tracking echocardiography offers prospective lead targeting, incorporating pathophysiological determinants of cardiac resynchronization therapy response. This review considers the key factors in defining optimum left ventricular lead location, emphasizing the role of myocardial scar. The use of speckle tracking echocardiography and the potential for this technique to be incorporated into routine practice to guide the implant strategy in an individual patient is discussed.