In children, as in adults, H1-antagonists are useful in the treatment of allergic rhinoconjunctivitis. Level 1 evidence for their efficacy in this disorder has been obtained in many well-designed pediatric studies. The widespread use of H1-antagonists in upper respiratory tract infections or otitis media in children is not supported by a strong scientific rationale. H1-antagonists are not harmful in children with asthma and, indeed, may have some beneficial effects in children with mild asthma. Their role in delaying or preventing asthma from developing in high-risk infants and toddlers is currently an important area of clinical investigation. The evidence base for their use in children with urticaria or atopic dermatitis still contains large gaps. First-generation H1-antagonists are presumed to be safe for use in infants and children. While they have undoubtedly been administered without apparent harm to millions in this age group, they impair CNS function far more commonly than is generally realized. Their use should be restricted to two uncommon situations: children with urticaria or atopic dermatitis whose pruritus is so severe that the sedation produced by an old H1-antagonist, such as hydroxyzine, is a benefit rather than a risk; and children with anaphylaxis who require intravenous diphenhydramine as adjunctive treatment to epinephrine and other modalities. Apart from these exceptions, in patients of all ages, second-generation H1-antagonists free from CNS adverse effects are clearly the medications of choice. Pediatric formulations of the new H1-antagonists cetirizine, fexofenadine, and loratadine are now available for use.