The successful application and optimization of cell transplantation will require quantitative engineering design and analysis of cells and materials in which relevant biological processes remain complex and incompletely defined. This report primarily reviews the engineering and material considerations in islet cell transplantation, including established biological constraints and biohybrid devices for cell delivery, as well as available barrier materials and the associated processing strategies directed at the control of solute transport, barrier permeability, and host responses at the biological-material interface. Also described are current areas of investigation with particular promise as enabling technologies for accelerating the clinical effectiveness of islet cell transplantation.