Dual antiplatelet therapy (DAPT) prevents recurrent ischemic events after an acute coronary syndrome (ACS) as well as stent thrombosis (ST) in patients with prior stent implantation. Nevertheless, these benefits are counterbalanced by a significant bleeding hazard, which is directly related to the treatment duration. Although DAPT has been extensively studied in numerous clinical trials, optimal treatment duration is still debated, mostly because of apparent inconsistencies among studies. Shortened treatment duration of 6 or 3 months was shown to mitigate bleeding risk compared with consensus-grounded 12-month standard duration, without any apparent excess of ischemic events. However, recent trials showed that a >12-month course of treatment reduces ischemic events but increases bleeding compared with 12 months. The inconsistent benefit of a longer DAPT course compared with shorter treatment durations is puzzling, and requires a careful appraisal of between-studies differences. We sought to summarize the existing evidence aiming at reconciling apparent inconsistencies among these studies, as well as thoroughly discuss the possible increased risk of fatal events associated with long-term DAPT. Benefits and risks of prolonging or shortening DAPT duration will be discussed, with a focus on treatment individualization. Finally, we will provide an outlook for possible future directions in the field.