Dual antiplatelet therapy (DAPT) is the gold standard for the antithrombotic management of patients with an acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Implementation of intensified or prolonged DAPT regimens has proven to lower the risk of ischemic events but at the expense of increased bleeding. Importantly, bleeding is a predictor of poor prognosis. Risk stratification and selection of tailored antiplatelet strategies to maximize the net clinical benefit in individual patients with ACS or undergoing PCI is therefore potentially beneficial. Recently, novel approaches including DAPT de-escalation or escalation have been proposed as possible alternatives to standard DAPT. These strategies, which are generally based on patient's risk profile, genetics, and/or platelet function have been proposed to offer more tailored treatments in patients with ACS or PCI, with the ultimate goal of providing adequate ischemic protection while mitigating the risk of bleeding. This review summarizes the available evidence on DAPT de-escalation or escalation (both guided and unguided) and discusses the practical implications of these strategies in the contemporary management of patients with ACS and/or undergoing PCI.