Zhang, PeipeiBookstaver, Michelle L.Jewell, Christopher M.Engineering cell surfaces with natural or synthetic materials is a unique and powerful strategy for biomedical applications. Cells exhibit more sophisticated migration, control, and functional capabilities compared to nanoparticles, scaffolds, viruses, and other engineered materials or agents commonly used in the biomedical field. Over the past decade, modification of cell surfaces with natural or synthetic materials has been studied to exploit this complexity for both fundamental and translational goals. In this review we present the existing biomedical technologies for engineering cell surfaces with one important class of materials, polyelectrolytes. We begin by introducing the challenges facing the cell surface engineering field. We then discuss the features of polyelectrolytes and how these properties can be harnessed to solve challenges in cell therapy, tissue engineering, cell-based drug delivery, sensing and tracking, and immune modulation. Throughout the review, we highlight opportunities to drive the field forward by bridging new knowledge of polyelectrolytes with existing translational challenges.en-USpolyelectrolytemultilayercell modificationsensing and signalingdrug deliveryvaccine and immunotherapysurface proteintissue engineeringregenerative medicineArticle