Advanced revascularization strategies continue to uncover a growing number of patients with symptomatic diffuse coronary artery disease. Transmyocardial laser revascularization (TMR) provides significant benefit in terms of improved quality of life and more complete revascularization for these difficult to treat patients when TMR is used as sole therapy or in combination with coronary artery bypass grafting. The safe clinical application of this important procedure relies on diligent perioperative management with appropriate patient selection, intraoperative care that avoids myocardial ischemia, and postoperative pain control along with expeditious reinstitution of antianginal medications. The treatment paradigms learned with the safe application of TMR should prove useful as new therapies to extend our revascularization options are developed.