Percutaneous coronary intervention (PCI) is one of the most commonly performed therapeutic procedure worldwide. In this chapter, the authors aim to provide an overview of the pharmacologic treatment strategies aimed at optimizing the safety and efficacy of PCI in contemporary practice. Several risk prediction models have been developed to allow for risk stratification of patients undergoing PCI. Estimating the individual risk of ischemic and bleeding complications permits personalized clinical decision-making, which is paramount in selecting the appropriate antithrombotic treatment strategy. Continuous refinements in stent technology have allowed broadening the scope of PCI to increasingly challenging patient subsets which, although well represented in real-world practice, have generally been excluded or under-represented in randomized studies. Therefore, the ischemia-bleeding trade-off of short vs prolonged DAPT remains somewhat uncertain. Recent evidence suggests new opportunities of implementing point-of-care techniques to modulate the intensity of DAPT based on individual physiologic and genetic assessment of platelet reactivity.