Aim: The purpose of this study was to systematically assess the quality of evidence supporting fluoride's alternatives for treating early enamel caries. Methods: A broad search strategy using PubMed and other sources was performed. For sensitive search strategy, we used MESH database and the following search queries: (‘‘Remineralization'' [Mesh] OR ‘‘Remineralisation'') AND (‘‘Caries'' [Mesh] OR ‘‘Decay'') AND (‘‘Fluoride''). Predetermined criteria were: parallel, randomized, controlled trial studies with 6 to 18 years old children. Results: 1919 articles from PubMed advanced search were initially revealed then 79 papers were picked up, in addition to 536 from other sources. One paper only removed as a duplicate (by the author, title and reference). The remaining articles were indicated for closer assessment. Out of 614 papers were screened by title, only 29 met the inclusion criteria of this review. Additional screening by abstract was done independently by the three researchers to result in 7 articles. Conclusion: From this review, there is moderate clinical evidence to support preventive agents as fluoride substitutes. This review suggests the use of resin infiltration and fluoridated Miswak as remineralizing agents.