In recent years, significant advances in enhancing the quantum yield (QY) of trivalent lanthanide (Ln3+) ion-based nanoparticles have been achieved through photosensitization, using host matrices or capping organic ligands as photosensitizers to absorb incoming photons and transfer energy to the Ln3+ ions. The Ln3+ ion-based nanoparticles possess several excellent fluorescent properties, such as nearly constant transition energies, atomic-like sharp transitions, long emission lifetimes, large Stokes shifts, high photostability, and resistance to photobleaching; these properties make them more promising candidates as next-generation fluorescence probes in the visible region, compared with other traditional materials such as organic dyes and quantum dots. However, their QYs are generally low and thus need to be improved to facilitate and extend their applications. Considerable efforts have been made to improve the QYs of Ln3+ ion-based nanoparticles through photosensitization. These efforts include the doping of Ln3+ ions into host matrices or capping the nanoparticles with organic ligands. Among the Ln3+ ion-based nanoparticles investigated in previous studies, this review focuses on those containing Eu3+, Tb3+, and Dy3+ ions with red, green, and yellow emission colors, respectively. The emission intensities of Eu3+ and Tb3+ ions are stronger than those of other Ln3+ ions; therefore, the majority of the reported studies focused on Eu3+ and Tb3+ ion-based nanoparticles. This review discusses the principles of photosensitization, several examples of photosensitized Ln3+ ion-based nanoparticles, and in vitro and in vivo biomedical fluorescent imaging (FI) applications. This information provides valuable insight into the development of Ln3+ ion-based nanoparticles with high QYs through photosensitization, with future potential applications in biomedical FI.