The first-line therapy for chronic urticaria is the second generation histamine H1 receptor antagonist. However, some patients with chronic refractory urticaria using regular doses of histamine H1 receptor antagonist have no obvious effect. So, we often combine histamine H1 receptor antagonist with non-antihistamine drugs to cure chronic refractory urticaria. According to clinical observation, the curative effect of combination therapy of chronic urticaria is superior to using histamine H1 receptor antagonist alone. The commonly used non antihistamine drugs include leukotriene receptor antagonist, glucocorticoid, tricyclic antidepressants, immunosuppressants, biologics, etc. But the non-antihistamine drugs have more side effects. It is recommended to weigh the pros and cons before using these drugs, and we should also pay attention to monitoring the occurrence of the side effects during using.