The duration and combination of dual antiplatelet therapy after coronary stent implantation, consisting of aspirin and a P2Y12 inhibitor, is among the most intensely investigated therapeutic strategies in cardiovascular medicine. While initial studies have mainly focused on the efficacy and safety of individual antithrombotic agents, the increased need for a personalized, risk-based approach to define the optimal duration of antithrombotic treatment according to the estimated ischemic and bleeding risk was then recognized. Recent recommendations for the optimal duration of antithrombotic combination therapies following coronary stent implantation in various clinical scenarios have substantially changed. The aim of the present article is to discuss the recent evidence from randomized clinical trials and observational studies with respect to antithrombotic treatment regimens in patients undergoing coronary artery stenting for stable coronary artery disease (CAD) or an acute coronary syndrome (ACS). We will focus on optimal treatment duration and a personalized approach based on ischemic and bleeding risk assessment.