Clopidogrel, being a potent platelet aggregation inhibitor, is used widely around the world to reduce cardiovascular risks in patients with stroke, myocardial infarction, and atherosclerosis. The aim of this review firstly focuses on a comprehensive update of chromatography determination of clopidogrel and its metabolites as well as in human plasma, Wistar rat plasma, and in pharmaceutical preparations. It has been described using TLC, HPLC/MS, RP-HPLC, and GC/MS methods. Secondly to localize the chromatography conditions for separation and quantification, this review provides detailed information on separation conditions for clopidogrel and its metabolites. A new HPLC method adjusted to our laboratory conditions was developed for the evaluation of assay and purity of clopidogrel in film-coated tablets.