Refinement of interventional techniques, adjunctive pharmacological therapy, and the introduction of drug eluting stents have fostered new interest for the percutaneous treatment of unprotected left main coronary artery (ULMCA) stenosis. Several observational registries, some randomized controlled trials and several meta-analyses have consistently shown no difference in mortality and myocardial infarction between percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery in patients with ULMCA stenosis, but a higher rate of target vessel revascularization in patients treated with PCI. As a consequence, PCI of ULMCA stenosis has been upgraded to class IIa or IIb indication in the current European or American College of Cardiology/American Heart Association practice guidelines. Although these results are promising, they do not still represent enough evidence for extending PCI of ULMCA stenosis to current clinical practice. The EXCEL trial will address the value of PCI in relation to CABG for the treatment of ULMCA stenosis in more than 2000 patients. A major breakthrough of the SYNTAX trial has been the demonstration of an interaction between the coronary complexity and the revascularization strategy, suggesting that optimal risk stratification is a key element when deciding the best strategy of revascularization in this high-risk group of patients. Multidisciplinary team approach remains essential to provide a balanced information to the patient and to offer the beast treatment option. © 2012 Wiley Periodicals, Inc.