A significant stenosis of the unprotected left main coronary artery remains a common condition and is associated with a high rate of adverse events, both early and at long term. Whereas in the era of balloon-only percutaneous transluminal coronary angioplasty (PTCA) a stenosis of the unprotected left main coronary artery was considered a contraindication to percutaneous revascularization, the introduction of stents, especially the recent development of drug-eluting stents, has convinced several interventional cardiologists to treat percutaneously this subset of patients with coronary artery disease. Several studies are now available on this topic, including a 1200-patient large meta-analysis, most suggesting favorable results for PTCA with drug-eluting stents in patients with unprotected left main stenosis at both early and mid term. The aim of this article is to provide an updated review on the clinical management and technical approach for the percutaneous treatment of unprotected left main stenosis, in light of our 10-year experience with this peculiar percutaneous procedure.