Since the early seventies with the work of Akira Fujishima on photocatalytic and superhydrophilic properties of titanium dioxide (TiO2), also known as the Honda–Fujishima effect, photocatalysis has been investigated and progressively implemented in cement-based materials towards the development of self-cleaning, air-purifying and antiseptic materials, buildings and infrastructure. Although important achievements have been obtained at the laboratory scale, their real scale application has had some limitations mainly due to the low efficiencies obtained during adverse environmental conditions. Therefore, this article presents the challenges and opportunities of using of titanium dioxide in cement-based materials towards the development of truly efficient sustainable building materials. First, TiO2 photocatalysis and its incorporation in cementitious materials are presented. Second, self-cleaning, air-purifying and antimicrobial properties are discussed in terms of the lab and pilot project results. Third, conclusions regarding the different multifunctional properties are given towards the real application of TiO2 photocatalysis. Particularly, complementary technologies and strategies are presented in order to increase the above-mentioned multifunctional properties.