Drug allergies are reported in approximately 10% of children and carry significant health and economic impacts. However, only a minority of these reported drug allergies are established on diagnostic workup. Classically, drug allergies were diagnosed by skin prick and/or intradermal tests. However, recent data reveal that a direct ingestion challenge is often an appropriate diagnostic strategy in cases of reported nonsevere reactions to penicillin derivatives in children. This article will review the prevalence, diagnosis, and management of the main culprits of pediatric drug allergies: antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). We will also review severe cutaneous adverse reactions to drugs in children.