Dexmedetomidine is a highly selective α2-adrenoceptor agonist that demonstrates anxiolytic and analgesic properties without inducing respiratory compromise, which makes it a suitable agent for procedural sedation and imaging studies. In our current case reports, intravenous dexmedetomidine infusion was used to provide sedation to 2 pediatric patients over more than 20 sessions of radiation therapy. On both occasions, dexmedetomidine provided adequate sedation without respiratory depression. However, the required dosage increased with repeated radiation therapy sessions.