Dexmedetomidine, an alpha-2 agonist approved only for sedation in adult intensive care patients, is increasingly used off-label in- and outside Europe in the pediatric setting for various indications such as to prevent agitation, as premedication in the form of intranasal, buccal and oral solution, as adjunct for elective surgery, as sedative for magnetic resonance imaging, as intraoperative analgesia, for extracorporeal shock wave lithotripsy, and as adjuvant to ropi- and bupivacaine for nerve blocks. Dexmedetomidine is also used intravenously at different intensive care units with the purpose of sedation of children. In this paper, we assess 51 minor trials in the form of 44 randomized controlled trials and 7 prospective observational studies in an attempt to update the available evidence on dexmedetomidine use in pediatrics. Furthermore, we discuss its potential indications, benefits and adverse effects. However, it is important to state that much of the existing evidence favoring dexmedetomidine in children is either extrapolated from adult studies or based on small randomized controlled trials and observational studies with their inherent methodological shortcomings and confounding factors. Based on the best current evidence dexmedetomidine is found suitable and safe for various indications. However, in order to discover its full potential, indications, dosing and safety profile for various ages and procedures, it should urgently be examined by conducting good quality pediatric trials. Finally, we provide the readers with guidance on how to apply and dose dexmedetomidine for pediatric sedation and for other indications.