Fever and pain in children, especially associated with infections, such as otitis media, are very common. In paediatric populations, ibuprofen and paracetamol (acetaminophen) are both commonly used over-the-counter medicines for the management of fever or mild-to-moderate pain associated with sore throat, otitis media, toothache, earache and headache. Widespread use of ibuprofen and paracetamol has shown that they are both effective and generally well tolerated in the reduction in paediatric fever and pain. However, ibuprofen has the advantage of less frequent dosing (every 6–8 h vs. every 4 h for paracetamol) and its longer duration of action makes it a suitable alternative to paracetamol. In comparative trials, ibuprofen has been shown to be at least as effective as paracetamol as an analgesic and more effective as an antipyretic. The safety profile of ibuprofen is comparable to that of paracetamol if both drugs are used appropriately with the correct dosing regimens. However, in the overdose situation, the toxicity of paracetamol is not only reached much earlier, but is also more severe and more difficult to manage as compared with an overdose of ibuprofen. There is clearly a need for advanced studies to investigate the safety of these medications in paediatric populations of different ages and especially during prolonged use. Finally, the recently reported association between frequency and severity of asthma and paracetamol use needs urgent additional investigations.