Anaphylaxis represents one of the most frequent medical emergencies in childhood. However, as compared to adults, drugs are less common triggers of anaphylaxis in children, with a frequency which is increasing  from infancy to adolescence. Deaths seldom occur, maybe because of the paucity of comorbidities in children.  Antibiotics and non-steroidal anti-inflammatory drugs  (NSAIDs) are the main elicitors in drug-induced anaphylaxis in children. Both immune-mediated (mainly IgE-mediated) and non immune-mediated may be involved. IgG-mediated and complement-mediated mechanisms has been also hypothesized. Correct management relies on a right diagnosis and prompt therapy. A proper work-up is also important to prevent further potentially fatal re-exposures to the same drug or other structurally similar molecules but also unnecessary avoidance of medications not representing the culprit of the episode.