Chirality is now a key area in the field of research. Researchers are well versed with analytical separations but at the same time, they are unaware of the growth in the field of chiral separation. According to the United States Food and Drug Administration (US FDA) guidelines, it is mandatory to separate chiral drugs before they are marketed. Chiral separation has gained importance in the last 10 years due to the differential biological responses of the enantiomers in chiral environment. Identical physical and chemical properties of the enantiomers pose a major challenge for the separation of chiral compounds. Further, bioanalytical method development is also necessary to throw light on the fate of separated enantiomers in biological environment. High Performance Liquid Chromatography (HPLC) and Capillary Electrophoresis (CE) are the most widely used techniques for such separation. Antihistamines are a class of drugs that are represented by a wide number of chiral compounds. Hence this review focuses on enantioseparation of chiral antihistamine drugs. It begins with a brief discussion about antihistamine drugs, chiral separation and its need for study, followed by a brief overview of the analytical and bio-analytical work carried out on different chiral antihistamine drugs. The analytical and bio-analytical techniques that are used include HPLC, CE and some new techniques.