Background: Urticaria is a skin disease characterized by pruritic edematous lesions also called wheals. Although these lesions are self-limited they may result in lowered quality of life index. By far, the most recognized mechanisms that trigger the progression of this condition are hypersensitivity reactions. As an herbal therapy, Plantago major has been named in several references of Persian traditional medicine with effective properties in ameliorating urticarial symptoms. In this study we aimed to investigate whether Plantago major has the potential to be used clinically in treatment of urticaria according to the current knowledge about the plant effects. Materials and Methods: A combination of "Plantago major" and other terms related to urticarial therapy such as "mast cell", "anti-inflammatory", "prostaglandin", "histamine" and "IgE" that may have possible role in progression or suppression of urticaria was searched in Google Scholar and PubMed as the reference databases. Results: Eleven articles discussing either the direct role of Plantago major or any of its constituents in urticarial related bimolecular pathways were selected. Conclusion: Review of the selected articles indicated that Plantago major can effectively suppress many of hypersensitivity reactions which are also contributors in the pathophysiology of urticaria development. Further clinical trials are needed to prove the efficacy of this herbal treatment.