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 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 practice guidelines. However, several critical issues should be properly addressed when pursuing a percutaneous strategy for the treatment of ULMCA stenosis, such as the use of IVUS for procedural guidance, assessment of disease location, optimal technique for distal ULMCA stenosis, risk of stent thrombosis, optimal duration of dual antiplatelet therapy, and the most appropriate strategy for post-procedure follow up. Multidisciplinary team approach remains essential to provide a balanced information to the patient and to offer the beast treatment option. © 2011 Wiley Periodicals, Inc.