Persistent luminescence nanoparticles (PLNPs) can realize nondestructive imaging, detection, diagnosis and treatment without background interference due to their unique and outstanding luminescence phenomena. In addition, the emission wavelength of PLNPs is determined by their luminescence center. Thus, Cr ³⁺-doped PLNPs (Cr-PLNPs) have attracted much attention in the biomedical field due to their near-infrared (NIR) light emission, good tissue penetrability, and ultra-strong persistent luminescence (PL) excited by NIR light. In this paper, we discussed the application of Cr-PLNPs to biological detection, imaging, and therapy, analyzed their problems, and pointed out their future research directions.