Over the past 30 years, restorative dentistry has seen a revolution in materials, restorative techniques, and patient priorities. This revolution has been made possible with the development of new resin-based materials which can be bonded to the tooth structure. Not all of these changes have been without controversy or concern, and some have raised questions about the biological safety of these new materials and techniques. It is the purpose of this review to present recent and relevant information about the biological risks and consequences of resin-tooth bonding and how these risks are affected by the material, its clinical properties, and its manipulation by the practitioner. These biological risks are complex and interactive, and are still incompletely defined. In broad terms, these risks can be divided into those stemming from the toxicological properties of the materials themselves (direct biological risks) and those stemming from microbiological leakage (indirect biological risks).