Coronary artery bypass grafting (CABG) decreases mortality in patients with significant left main (LM) coronary artery disease and for years remained the therapy of choice for patients with this ominous lesion. Advances in percutaneous coronary intervention (PCI) have enabled it to become an alternative to CABG. The results of observational registries and randomized comparisons have shown the safety and efficacy of PCI in appropriately selected patients with low or intermediate angiographic risk scores. Furthermore, the use of physiological measures of flow limitation and the use of intracoronary imaging techniques has added benefit and improved outcomes. The use of fractional flow reserve to more accurately evaluate the significance of intermediate lesions and guide the extent of revascularization has been an important refinement. Intravascular ultrasound and optical coherence tomography assessment of optimal stent deployment has led to reductions in restenosis. Newer generation stents, combined with improvements in specific techniques, especially at the LM bifurcation have extended PCI to more complex anatomic scenarios. The availability of left ventricular support devices in patients with complex coronary anatomy and severely depressed left ventricular function has added a margin of safety to LM and multivessel intervention. Randomized comparisons of CABG with PCI in carefully selected patients, using contemporaneous surgical and interventional techniques and optimal medical therapy, will further aid heart teams in the decision-making process. In conclusion, this review will give a concise overview of the management of unprotected LM disease.