In the last decade, most publications on the mechanical properties of dental calcified tissues were based on nanoindentation investigation. This technique has allowed a better understanding of the mechanical behavior of enamel, dentin, and cementum at a nanoscale. The indentations are normally carried out using pointed or spherical indenters. Hardness and elastic modulus are measured as a function of indenter penetration depth and from the elastic recovery upon unloading. The unique microstructure of each calcified tissue significantly contributes to the variations in the mechanical properties measured. As complex hydrated biological composites, the relative proportions of the composite components, namely, inorganic material (hydroxyapatite), organic material, and water, determines the mechanical properties of the dental hard tissues. Many pathological conditions affecting dental hard tissues cause changes in mineral levels, crystalline structures, and mechanical properties that may be probed by nanoindentation. This review focuses on relevant nanoindentation techniques and their applications to enamel, dentin, and cementum investigations.