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The endodontic management of permanent immature teeth is fraught with challenges. Although treatment modalities for vital pulp therapy in these teeth provide long-term favorable outcome, the outcomes from the treatment of pulp necrosis and apical periodontitis are significantly less predictable. Immature teeth diagnosed with pulp necrosis have been traditionally treated with apexification or apexogenesis approaches. Unfortunately, these treatments provide little to no benefit in promoting continued root development. Regenerative endodontic procedures have emerged as an important alternative in treating teeth with otherwise questionable long-term prognosis because of thin, fragile dentinal walls and a lack of immunocompetency. These procedures rely heavily on root canal chemical disinfection of the root canal system. Traditionally, irrigants and medicaments have been chosen for their maximum antimicrobial effect without consideration for their effects on stem cells and the dentinal microenvironment. Translational research has been crucial to provide evidence for treatment modifications that aim to increase favorable outcome while steering away from common pitfalls in the currently used protocols. In this review, recent advances learned from translational research related to disinfection in regenerative endodontics are presented and discussed.