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Regenerative endodontic procedures for immature teeth with pulp necrosis have gained a lot of interest. Basic scientific research has documented the potential for dental pulp regeneration in preclinical studies. A number of case reports and case series have shown the control of clinical infection and increases in thickness and length of the roots. Preoperative infection is an important factor that predicts outcome in nonsurgical endodontic treatment in mature teeth and seems to also be an important determinant of outcome in treating immature teeth. However, antimicrobial strategies for the immature tooth in which pulp regeneration is contemplated are different from those used in mature cases. This is because of the interest in disinfecting the root canal to a higher level to promote tissue growth without disrupting the bioactive potential of root dentin and the viability of stem cells from which the regenerated tissue would develop. This review addresses the factors involved in making clinical decisions in this area in light of the information available on the microbiology of endodontic infections, the efficacy to antimicrobial strategies, and the outcomes of regenerative and alternative procedures.