Antiplatelet therapies have reduced the frequency of adverse events associated with plaque rupture in several clinical situations. These therapies include established antiplatelet agents (such as aspirin, clopidogrel, or glycoprotein IIb/IIIa inhibitors) as well as new agents (such as prasugrel and ticagrelor). In this Review, we address the most important adverse events of antiplatelet therapy, including hemorrhage, hematologic reactions, and dyspnea. We discuss strategies to reduce the incidence of complications and outline potential methods to manage adverse reactions. Interactions between antiplatelet agents and other drugs--such as proton-pump inhibitors, calcium-channel blockers, statins, warfarin, or NSAIDs--are also addressed, as well as specific issues relating to the use of antiplatelet therapies in elderly patients.