Antihistamines have an important role in dermatology. In order to understand how antihistamines work, effects of histamine should be examined first. Histamine was first defined in 1920s and was shown to take part in the pathogenesis of diseases such as urticaria, anaphylaxis, asthma, and allergic rhinitis. The main goal in the treatment of urticaria and other diseases related to histamine is to keep this powerful mediators effects under control. So many antihistamines have been presented to the market since 1942 and still, new compounds are being developed. For years, antihistamines have been categorized as first, second and third generation. In this text, a review of the action mechanism of antihistamines and the new antihistamines will be presented.