Our understanding of the pathophysiology of allergy has moved to the molecular level, while study of epidemiology and genetics has revealed risks of developing allergies based on environmental and genetic profiles, and pharmacoeconomic data have enabled accurate measurement of the immense burden of allergic disease. These advances in allergy research have affected its management, particularly the search for new antiallergy therapies. New therapies should intervene in the systemic allergy inflammatory cascade and provide clinical efficacy that extends to multiple allergic disease states. In addition, these new therapies should present no additional safety issues, offer improvements over existing therapies, and have an impact on disease-impaired quality of life. In vitro studies show that desloratadine, a new, once-daily, nonsedating, selective histamine H1-receptor antagonist, blocks the systemic allergy cascade at multiple points. Desloratadine 5 mg once daily relieves the symptoms of chronic idiopathic urticaria and of both seasonal (SAR) and perennial allergic rhinitis. In patients with concomitant asthma and SAR, asthma symptoms are relieved and β2-agonist medication use is decreased by desloratadine. Unlike many other second-generation histamine H1-receptor antagonists, desloratadine provides the added benefit of efficacy against nasal obstruction in SAR. Desloratadine improves quality of life by decreasing the impact of allergic symptoms on sleep and on daily activities.