Antihistamines are widely used in allergic diseases such as urticaria and allergic rhinitis, mainly by reverse excited histamine and anti-allergic effects. Antihistamines are generally safe, but there may be some adverse reactions like cardiotoxicity, central inhibition, anticholinergic effects, etc. And there are also individual differences in clinical practice. The concept of individualized medicine has been deeply rooted in people's minds since it was put forward. In recent decades, pharmacogenomics has been developing rapidly, which provides new ideas for the occurrence of individual medication. Gene polymorphism in the metabolic enzyme, transports, and target receptors have been shown to affect the application of antihistamines. Besides, recent evidence suggests that genetic polymorphisms influence urticaria susceptibility and antihistamine therapy. Here, we summarize current reports of this area, aim to contribute to the future research and clinical guidance of antihistamine personalized medicine.