White spot lesions are a common complication after orthodontic treatment. The aim of this systematic review was to investigate which remineralizing agents are effective for the treatment of white spot lesions after orthodontic treatment. According to predetermined criteria, 4 databases were searched for appropriate studies. References of the selected articles and relevant reviews were searched for any missed publications. Seven randomized controlled trials were selected as eligible studies, and only qualitative analyses were performed because of the diversity of the interventions and outcome measures. Two studies showed significant effects of 2 different fluoride preparations: one with a small sample size and several methodologic deficiencies, and the other using only nonconventional detection methods (ie, DIAGNOdent pen, KaVo, Biberach, Germany) to assess white spot lesions. Two studies involved casein phosphopeptide-amorphous calcium phosphate, which seemed to be effective for the regression of white spot lesions. However, the statistical analysis in 1 study was based on the tooth surfaces instead of the patient, and the visual examination used in the other study to assess the white spots was not reliable. Based on the literature, there is a lack of reliable evidence to support the effectiveness of remineralizing agents for the treatment of postorthodontic white spot lesions. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.