Because of more and more accurate cardiovascular prevention programs and the increasing mean age of the general population, the use of antiplatelet treatments is progressively increasing in the last years. Moreover, the wide-spread use of bare-metal stents (BMS) and drug-eluting stents (DES) significantly increased the number of subjects with the need of a combined antiplatelet treatment: Aspirin (ASA) and Clopidogrel (CLO. Within the first year after coronary stenting, approximately 5% of patients needs to undergo non-cardiac surgery interventions. In such patients, current guidelines suggest to stop antiplatelet agents 7-10 days before surgery to avoid the risk of increasing blood loss. On the other hand, it has been shown that the risk of surgical bleeding, if antiplatelet drugs are continued, is lower than that of coronary thrombosis if they are withdrawn. Thus, an accurate stratification of the population according to the thrombotic risk is needed and the bleeding and the thrombotic risk should be considered in parallel. Although a growing amount of recommendations have been released by several Societies, the perioperative handling of antiplatelet drugs still represents a major concern in clinical practice. In this review we report the major literature data about the perioperative handling of antiplatelet drugs. Moreover, in order to describe future treatment perspectives and to identify valuable alternatives to current antiplatelet agents in the perioperative period, pharmacokinetic and pharmacodynamic characteristics of newer antiplatelet drugs are reported and analyzed.