The use of resin composites and adhesives in dental restorations is ubiquitous. However, the longevity of resin composites is less than that of comparable restorative materials, mainly because of higher fracture rates and greater prevalence of secondary caries. Dental resin composites and adhesives contain ester links, which are vulnerable to biochemical hydrolysis by esterase activity from human saliva and bacteria. In this article, we review biodegradation processes that occur in the oral cavity and their contribution to the premature failure of resin composites. Biodegradation causes deterioration of resin composite bulk and the composite-tooth interface and releases by-products, such as methacrylic acid, triethylene glycol and bishydroxy-propoxy-phenyl-propane. These by-products have been shown to affect cariogenic bacterial growth and virulence. A compromised restoration-tooth interface allows saliva and oral bacteria to infiltrate the spaces between the tooth and the composite, exacerbating the effects of biodegradation, undermining the restoration and leading to recurrent caries, hypersensitivity and pulpal inflammation. It is important to consider the biochemical stability of these materials to advance their chemistry beyond the current formulations and conceive more biochemically stable and better-performing dental resin composites and adhesives.