Nanotechnology entered dentistry with the advancements in dental materials mainly composites and bonding agents. The development of nanodentistry will alter the focus to more specific diagnosis and treatment modalities for the maintenance of perfect oral health. Many studies have demonstrated that nanomaterials can exhibit inflammatory responses and promote DNA damage through direct or indirect mechanisms. The key point is that different nanomaterials exhibit a variety of toxicity depending upon the type of living organism. Future research must be based on the development of methodologies for nanomaterials control and to minimize nanomaterial hazard. This review provides an overview of the challenges faced by nanodentistry and related toxicology issues.