Background Antihistamines are used for the treatment of allergic rhinitis, allergic conjunctivitis, chronic spontaneous urticaria and atopic eczema. Objective To study the reports of adverse drug reactions (ADRs) in children using antihistamines to provide prescribers with an overview of the possible toxicity. Design We studied ADRs in children reported to the Netherlands Pharmacovigilance Centre Lareb in the years 1991–2014, assessed the Naranjo score and, when possible, computed the reporting OR. Results Serious ADRs included one death (malignant neuroleptic syndrome), cardiac arrhythmia (one case) and convulsions (three cases). Skin eruptions, headache and somnolence were the most frequently reported ADRs. Aggression and agitation were also reported. Conclusions Toxicity can occur with second-generation antihistamines. The main toxicity relates to skin eruptions and central nervous system problems.