This chapter focuses on the genetic determinants of clopidogrel response, a highly heritable phenotype. A candidate gene approach identified several polymorphisms involved in drug absorption or metabolisation but the contribution of these genetic variants to the variability of clopidogrel response is small, challenging the implementation of routine genetic testing for the personalization of antiplatelet therapy. Next generation sequencing will provide a better DNA coverage than genome wide association studies and certainly improve our understanding of the genetic basis of clopidogrel response variability.