Allergic diseases are responsible for substantially more disability than is generally realized. Allergic rhinitis alone results in 3.5 million lost workdays and 2 million missed school days in the United States each year. Comorbid conditions such as asthma and sinusitis can be disabling as well, resulting each year in more than 10 million missed school days and more than 73 million days of restricted activity, respectively. Antihistamines continue to be the mainstay of treatment for allergic disorders. In the case of the first-generation antihistamines, however, the treatment may well be worse than the disease. Although these agents are effective H(1)-receptor antagonists, they are also highly lipophilic and readily cross the blood-brain barrier, causing considerable sedation. The second-generation agents are more lipophobic and possess different ionic charges than the first-generation antihistamines. As a result, they are far less likely to cross the blood-brain barrier and, for that reason, cause little if any sedation. In a recent comparative trial, subjects who were treated with the first-generation agent diphenhydramine were found to have significant performance deficits on tests of divided attention, working memory, vigilance, and speed. By contrast, subjects who were treated with the second-generation antihistamine loratadine performed as well as subjects who were treated with placebo. The sedative effects of the first-generation agents persist well into the next day and thus can potentially interfere with daytime performance and safety even when taken the night before. It is therefore recommended that patients whose occupations require vigilance, divided attention, or concentration receive only second-generation antihistamines.