AbstractPurposeThis review integrated the current literature on diffusion of whitening agents, their interactions with stain molecules, and changes to the surface, with the aim of establishing a better understanding of the mechanism underlying tooth whitening.Materials and MethodsAn electronic PubMed database search, with combinations of the following terms was performed: Tooth Bleaching, Tooth Bleaching Agent, Hydrogen Peroxide, Pharmacokinetics, Tooth Permeability, Oxidation‐Reduction, Tooth Demineralization, and Color.ResultsTooth whitening is a dynamic process that involves diffusion of the whitening material to interact with stain molecules and also involves micromorphologic alterations on the surface and changes within the tooth that affect its optical properties. The interaction seems not to be limited to stain molecules, but rather an affinity‐based interaction process that also accompanies effects on sound enamel and dentin structures.ConclusionsThis review underlines that supervision by dental health professionals as recommended by the American Dental Association (ADA) Council on Scientific Affairs is critical to achieving a successful and safe whitening outcome.Clinical SignificanceThe mechanism that underlies tooth whitening with the use of peroxide‐based materials is a complex phenomenon encompassing diffusion, interaction, and surfaces changes within the tooth. Therefore, supervision by dental health professionals as recommended by the ADA Council on Scientific Affairs is imperative to achieve a successful and safe whitening outcome.