Despite increasing evidence of hemodynamic benefit and long-term improvement in clinical status of congestive heart failure (CHF) patients with left ventricular and biventricular pacing, the risks and technical limitations of placing a permanent left ventricular pacing lead have prevented widespread clinical adoption of this therapy. Results of this and other recent investigations suggest it is necessary to target specific sites on the left ventricle to maximize hemodynamic benefit. However, limitations and variations of coronary vein anatomy, as well as patient safety, lead dislodgement, pacing thresholds, lead handling, and ease-of-use issues, present technical challenges for current transvenous permanent pacing lead designs. However, a new transvenous lead system based on an over-the-wire design appears to solve many of these problems and has proved feasible in acute clinical studies.