Fever usually is a physiological response to infectious/inflammatory acute events. Namely, fever has positive benefits contrasting noxious agents. However, when fever causes discomfort, it is better to relieve symptoms associated to fever. Antipyretics mainly are non-steroidal anti-inflammatory agents (NSAIDs) and acetaminophen. The NSAIDs class includes many molecules. The most used NSAID to relieve fever is ibuprofen. However, ketoprofen also provides interesting pharmacological characteristics. In particular, salifying ketoprofen with lysine, such as ketoprofen lysine salt (KLS), provides a better and quicker absorption then acid ketoprofen and reduces side effects. The present paper considers the comparative pediatric studies between ketoprofen or KLS and other antipyretics, mainly concerning ibuprofen and acetaminophen. The results showed that ketoprofen and KLS are valuable option in managing children with fever.