Although fever is a beneficial host response, it is an important cause of anxiety for parents and doctors. The quest for effective treatment has led to new combination regimens of antipyretic drugs for febrile children. These are popular among caregivers and healthcare providers,1 2 3 4 but they have been tested in clinical trials only recently.4 5 6 7 8 The new regimens consist of combinations of ibuprofen and paracetamol (acetaminophen) given at variable time schedules. The main concern about these treatments is safety, because they may increase the risk of renal toxicity, as a result of reduced glutathione in the kidney and tubular necrosis,9 10 or the risk of infection with invasive group A streptococci.11 We therefore need to know whether these combinations are more effective than, and as safe as, monotherapy in children with fever.