Introduction: White spot lesions are the first clinical sign of dental caries, and they occur frequently in patients with orthodontic appliances. Currently, there are no systematic reviews that have evaluated fluoride varnish compared with other methods to prevent or arrest the development of dental caries. The aim of this systematic review (SR) was to evaluate the effectiveness of the use of fluoride varnish compared with other methods to prevent or arrest initial lesions of caries in patients with corrective orthodontics. Methods: A search was conducted for articles in the MEDLINE, EMBASE and Google Scholar databases. This SR included randomized clinical trials and prospective interventional studies that used fluoride varnish for the prevention and/or arrest of white spot lesions in orthodontic treatment or during the 3-month period after removal of orthodontic fixed appliances. To assess the risk of bias in the studies, we used the Cochrane collaboration tool. Results: The search strategy showed 115 possible eligible articles, and we included 10 articles in this SR. The reviewed studies showed high and moderate methodological quality. Four studies out of 10 agreed that fluoride varnish is as effective as the advised and guided oral hygiene technique. Overall, most of the included studies did not show significant advantages to fluoride varnish application in terms of preventing the development of white spots around orthodontic brackets when the patients were submitted to regular professional oral hygiene control. Conclusions: Fluoride varnish is an effective material to prevent and arrest white spot lesions in patients with orthodontic treatment.