Immobilized enzymes are useful in the development of techniques for analytical chemistry measurements, primarily because of the specificity of enzymes for given substrates. In the case of glucose an in vivo assay is needed for closed loop operation of an artificial pancreas insulin delivery system. Several enzymatic methods are available for in vitro determinations of glucose, but only two or three of these methods hold any promise of adaptation for in vivo use. The most promising enzymatic approaches include the use of immobilized glucose oxidase in conjunction with 1) an oxygen electrode to give an amperometric output or 2) a reference electrode to give a potentiometric output. The use of glucose oxidase or other D-glucose-specific enzymes in conjunction with sensitive thermistors to measure the heat of reaction may also be a feasible method. The two most promising approaches are described in terms of their feasibility for continuous measurement of blood glucose levels in vivo without the necessity of withdrawing body fluids for the assay.