The most common risks related to platelet inhibitor therapy are bleeding, drug-drug interactions and therapeutic failure. The new substances prasugrel and ticagrelor are more potent platelet inhibitiors than clopidogrel. This reduces the incidence of ischemic events, but also potentially increases the bleeding risk. Clopidogrel therapy has up to 20% non-response rates, which can partially be explained by genetic polymorphisms and drug-drug interactions. Currently no evidence exists that ticagrelor or prasugrel efficacy is affected by genetic polymorphisms. The therapy in patients at risk still has to be carefully adapted to minimize adverse events. Patients older than 75 years and/or weighing less than 60 kg should receive a reduced dose of prasugrel. The combination of ticagrelor with strong cytochrome-P450-3A4 inhibitors is contraindicated.