Caries is a very common, multifactorial disease, in which biofilms on the tooth surface (a.k.a. dental plaque) play a key role. Dental plaque is usually healthy, however when the microbial composition of the dental plaque changes, it can become cariogenic in nature. In this chapter, an historic overview is provided of different hypotheses developed to explain the relation between dental plaque and caries. Currently, the ecological plaque hypothesis is generally accepted. This hypothesis explains ecological changes relation to increased caries risk by environmental changes caused by dietary habits. Based on this hypothesis, prevention and treatment options can be explained.