Critical lesion of the unprotected left main coronary disease carries a tremendous mortality burden, often associated with a diabetes status or multivessel disease, with coronary artery bypass grafting being the standard treatment for over 40 years. Percutaneous coronary intervention with drug eluting stents should be taken into consideration and could be a better option for patients with low SYNTAX score as validated by the recently published studies. This review summarizes the major randomized clinical trials and meta-analyses concerning the debate regarding percutaneous coronary intervention with drug eluting stents versus coronary artery bypass grafting for unprotected left main coronary disease, along with the latest European and American revascularization guidelines and tries to shed light on this matter. The most results advocate that there is no convincing difference in survival rate for both therapies, especially in patients with isolated left main disease but with fewer major ischemic events for coronary artery bypass grafting when compared with percutaneous coronary intervention in multivessel coronary artery disease, at the rate of a higher stroke incidence. The gaps in evidence are also highlighted, especially the lack of randomized clinical trials with new generation drug eluting stents versus coronary artery bypass grafting or those regarding the best revascularization strategy for an acute coronary syndrome when unprotected left main coronary disease is involved.