The management of severe left main (LM) disease remains controversial and continues to evolve as new evidence emerges. Patient selection for coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) relies on both predicting mortality with CABG from clinical characteristics using the Society of Thoracic Surgeons (STS) risk score and anatomical complexity, using the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score. LM stenting techniques continue to evolve; for bifurcation lesions, the use of the double-kiss crush technique may reduce the incidence of late target vessel revascularization. In patients with acute coronary syndrome (ACS) complicated by cardiogenic shock, PCI is likely the first-line option in those with anatomically amenable disease, whereas all other stable non-ST-elevated ACS should be treated similar to stable ischemic heart disease. Outcomes comparing CABG and PCI have been recently examined in 2 large randomized clinical trials. In general, early outcomes of periprocedural myocardial infarction and stroke favoured PCI or were not different from outcomes with CABG. However, the conclusions of both trials are at present discordant with respect to late major adverse cardiac and cerebral events; additional follow-up of the trial patients is important for informed patient decision making. The appropriate mode of revascularization should be selected according to patient clinical characteristics and the complexity of the coronary lesions according to European and American guidelines. In those with low or intermediate SYNTAX scores, particularly with high surgical risk, PCI may be preferred to CABG in most other scenarios. A multidisciplinary heart team is recommended to help individualize revascularization decisions.