Dental caries is a multifactorial, bacterial, chronic infection that affects millions of people in the world and has become a public health problem. Also referred to as tooth decay, this disease is one of the most common disorders throughout the world, second only to the common cold. Dental caries is the most common chronic childhood disease in the United States and is 5 to 7 times more common than asthma. According to the World Oral Health Report in 2003, dental caries affect 60-80% of school children and a vast majority of adults. Dental caries is a chronic bacterial infection of the hard tissue of the tooth that is characterized by alternating phases of demineralization and remineralization. Dental decay can lead to significant pain and dysfunction that can interfere with basic functions such as eating, sleeping, and speaking. If left untreated, dental caries can result in cavities forming and eventually tooth loss. Although the prevalence and severity of dental caries has decreased over the years, this disease can be better controlled with proper fluoride exposure. Fluoride therapy has become the cornerstone strategy in the prevention of dental caries development and progression. With fluoride being available in various forms, fluoride exposure and/or treatment has greatly increased and has led to decreased incidences of dental caries. Fluoride has the ability to control the initiation and progression of carious lesions, mainly through the promotion of remineralization and the reduction in tooth enamel demineralization. Whether administered systemically or topically, the use of fluoride has proven to be effective in reducing the prevalence of dental caries. The aim of this review is to compare the topical methods of fluoride therapy with systemic applications. The goal is to evaluate the various forms of fluoride treatments based on cost effectiveness, safety, concentration and dosage of fluoride, ease of application, and accessibility to the community. This review will also identify the populations that are most susceptible to dental caries. The purpose of this review is to examine the benefits and risks of the various options of fluoride treatments in order to determine which would be the most the effective, safe, and efficient means of preventing dental caries in high risk populations. Based on the literature review, it was determined that the populations with the greatest risk for dental caries comprised of young children who were from lower socioeconomic backgrounds and elderly adults over the age of 65. After comparing the various forms of fluoride therapies, it was found that systemic fluoride treatments, mainly water fluoridation, would be the most effective in preventing dental caries in high caries risk populations.