Acute nociceptive pain management in children is a major public health concern. Effective and safe pain treatment is essential, but safety data cannot be simply extrapolated from adults to children due to pharmacokinetic and pharmacodynamic specificities. In addition, the frequent absence of child-specific data, the difficulty to assess drug tolerability, and the infants' inability to communicate properly and voluntarily report adverse drug reactions make children more vulnerable to safety issues. Awareness of the possible toxicity of analgesics is important but should not lead to suboptimal dosing and underuse of analgesia. A better assessment and individualization of treatment should allow effective prescribing of analgesics in more secure conditions. This article aims to review the safety of acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids in children and the precautions that should be taken.