The population of the world is aging. A greater proportion of older people are retaining increasing numbers of natural teeth. Aging is associated with changes in oral architecture and muscle weakness, making personal oral hygiene more difficult, particularly for the oldest and most frail individuals. Furthermore, there is exposure of root dentin with its higher pH for demineralization in addition to enamel as a substrate for caries. Aging is also associated, for many in the developed world, with taking multiple medications, with the associated risk of dry mouth. These variables combine to increase caries risk in older vulnerable populations. Caries occurs on both the crowns of teeth (predominantly around existing restorations) and the exposed roots. Prevention needs to be aggressive to control disease in this combination of circumstances, with multiple strategies for limiting the damage associated with caries in this population. This paper explores the evidence that is available supporting preventive strategies, including fluorides in various forms, chlorhexidine, and calcium phosphate supplementation.