The ability to measure glucose noninvasively in human subjects is a major objective for many research groups. Success will revolutionize the treatment of diabetes by providing a means to improve glycemic control, thereby delaying the onset of the medical complications associated with this disease. This article focuses on the current state of the art and attempts to identify the principal areas of research necessary to advance the field. Two fundamentally different approaches are identified for the development of noninvasive glucose sensing technology. The indirect approach attempts to measure glucose on the basis of its effect on a secondary process. The direct approach is based on the unique chemical structure of the glucose molecule. Advances for each approach are limited by issues of selectivity. Several critical parameters are discussed for the direct approach, including issues related to the optical path length, wavelength range, dimensionality of the multivariate calibration model, net analyte signal, spectral variance, and assessment of the chemical basis of measurement selectivity. A set of publication standards is recommended as a means to enhance progress toward a successful noninvasive monitor.