White spot lesions (WSLs) are one of the most common adverse effects following comprehensive fixed orthodontic treatment. The purpose of this review was to evaluate recent studies addressing the prevention and treatment of these lesions. Electronic databases were searched for English-written studies published between 2015 and October 2020 involving randomized clinical trials aiming at prevention or treatment of orthodontically induced WSLs using the following keywords in their title or abstracts: randomized clinical trial OR randomized controlled trial AND white spot OR caries OR demineralization OR decalcification OR remineralization. From the 23 papers which met the inclusion criteria, 11 were on preventive methods, while 12 addressed treatment protocols. However, most of the reviewed studies had a high risk of bias. The results of this review strongly support the importance of oral hygiene observation in preventing WSLs. Sodium fluoride varnish 5% was confirmed to be effective in the treatment of these lesions, as well as in the prevention of WSLs in patients with suboptimal oral hygiene. In addition, immediate CO2 laser irradiation after bonding can effectively prohibit formation of WSLs during orthodontic treatment. The literature also illustrates a promising masking effect of resin infiltration for the treatment of WSLs. However, little scientific evidence supports the effectiveness of Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) against WSLs, although more clinical trials with long-term follow-up are needed. Oral hygiene maintenance is crucial in the prevention of WSLs, and 5% sodium fluoride varnish and CO2 laser irradiation are recommended in patients with compromised oral hygiene. In the case of WSL formation, fluoride varnish and resin infiltration are effective treatment modalities.