Onset of action for relief of allergic rhinitis symptoms is of clinical significance to both the physician and the patient. Using either subjective or objective methods, the onset of action after a single, oral dose of an antihistamine can be measured. Multicenter studies, outdoor studies, and pollen challenge systems have been used to measure the onset of action. A literature search from 1985 to May 2002 was performed. All published, randomized, placebo-controlled clinical studies pertaining to the onset of action for relief of allergic rhinitis symptoms after a single, oral dose of a second-generation antihistamine (not combined with a decongestant) including cetirizine, desloratadine, fexofenadine, and loratadine, were reviewed. The onset of action for cetirizine ranged from 59 minutes to 2 hours and 6 minutes and for loratadine onset of action ranged from 1 hour and 42 minutes to none identified during the duration of the study. Cetirizine had a shorter onset of action than loratadine for all comparisons. Fexofenadine had an onset of action within 60 minutes. The literature search did not reveal any published onset of action studies for desloratadine. The onset of action for a given second-generation antihistamine depends on how it is defined and subsequently measured.