Clopidogrel inhibits platelet action through the P2Y12-ADP receptor in an irreversible manner. Plasma levels of the active drug and thus the drug effect exhibit large individual variation. Part of the variation is explained by genetic reasons, but drug interactions may also have an effect on the response. The obtained efficacy is lower than anticipated in as many as 30% of the patients. The poor drug response is associated with an increased risk of cardiovascular events. Measurement of clopidogrel resistance with laboratory studies is challenging. Several methods have been developed and are becoming available for clinical use.