Coronary artery bypass grafting (CABG) has been considered the standard therapy for unprotected (nonrevascularized) left main coronary disease (ULM). However, increasing experience with ULM percutaneous coronary intervention (PCI) has resulted in high procedural success and favorable early and late clinical outcomes. In particular, reduction in clinical restenosis with drug-eluting stents, evolution of procedural technique, and demonstration of favorable outcomes from comparative trials with CABG have promoted consideration of PCI as an alternative revascularization strategy in selected patients with ULM disease. This review summarizes the results from comparative studies examining PCI versus CABG for ULM disease, discusses changing indications for ULM PCI and identifies outstanding issues that must be considered before further advancing treatment recommendations.