Persistent luminescence materials (PLMs) are a class of unique luminescent materials that can remain luminescent for a few milliseconds to days without constant excitation. By virtue of the super long decay time, PLMs have been extensively explored in biosensing and bioimaging applications to elimin ate autofluorescence interference and improve signal-to-noise ratio in complex samples and tissues. However, nude PLMs often suffer from the poor stability, selectivity, and biocompatibility in biological system and in vivo, which greatly impedes their applications in biomedicine and bioanalysis. Remarkably, surface modification is a viable solution that endows PLMs with span-new features and can make PLMs suitable for organisms by altering PLMs' interaction with biological system. In this review, commonly used strategies for surface modification of PLMs are briefly introduced, and the applications of surface modified PLMs in biosensing and bioimaging as well as their challenges are summarized. Qiang Luo (top left) received his B.S. degree in chemistry from Lanzhou University in 2018. He is currently a master student under the supervision of Prof. Quan Yuan at Hunan University. His research interests include the development of functional nanomaterials for biosensing and bioimaging. Wenjie Wang (top right) received his B.S. degree from North China Electric Power University in 2018. He is currently a master student under the supervision of Prof. Quan Yuan at Hunan University. His research interests include the synthesis of inorganic nanomaterials for biological application. Jie Tan (bottom left) earned her Ph.D. degree from Zhejiang University in 2016. Then she joined the team of Prof. Weihong Tan in Hunan University as a postdoctoral fellow. Currently, she is an associate professor at Hunan University. Her main research interest is the design of chemically modified nucleic acids for biosensing. Quan Yuan (bottom right) received her B.S. degree from Wuhan University and Ph.D. degree from Peking University. Afterwards, she worked as a postdoctoral researcher in the group of Prof. Weihong Tan at University of Florida. Currently, she is a professor in Hunan University. Her research interests are the construction of nucleic acid nanomaterials and related biomedical applications.