Possibilities for engineering of fluorescent micro/nanoscale devices for glucose sensing are presented. A description of the potential for clinical use is given in terms of overall concept, current knowledge, advantages of the fabrication approach proposed, and challenges that must be addressed prior to clinical use. Deployment of micro/nanoparticles in the dermis may allow transdermal monitoring of glucose changes in interstitial fluid. Using electrostatic self-assembly, an example of nanotechnology for fabrication, two types of sensors are being studied: (1). solid nanoparticles coated with fluorescent enzyme-containing thin films and (2). hollow micro/nanocapsules containing fluorescent indicators and enzymes or glucose-binding proteins. Nanoengineering of the coated colloids and microcapsules allows precision control over optical, mechanical, and catalytic properties to achieve sensitive response using a combination of polymers, fluorescent indicators, and glucose-specific proteins. Challenges to in vivo use include understanding of material toxicity and failure modes, and determining methods to overcome fouling, protein inactivation, and material degradation.