Desloratadine is a once-daily, non-sedating, non-impairing, selective histamine H1-receptor antagonist. It relieves the symptoms of seasonal allergic rhinitis, perennial allergic rhinitis and chronic idiopathic urticaria by blocking multiple critical steps in the systemic allergic cascade and downregulating key allergy-induced inflammatory mediators. It also relieves asthma symptoms and decreases rescue medication use in patients with seasonal allergic rhinitis and comorbid asthma. Numerous clinical studies have demonstrated that desloratadine is safe, well tolerated and free of serious cardiac effects. Pharmacokinetic studies have demonstrated a low propensity for drug-drug or drug-food interactions. This review outlines the mechanism of action, efficacy and safety of desloratadine for the treatment of allergic inflammatory disorders.