Near-infrared spectroscopy has proven to be one of the most promising techniques for the development of a noninvasive blood glucose monitoring system for diabetic patients. In this work, Fourier transform infrared (FT-IR) transmission measurements of the combination band region (4000-5000 cm-1) were analyzed for samples containing glucose (analyte) in a matrix of bovine serum albumin and triacetin (models for proteins and fats), all spanning physiological levels relevant for a diabetic patient. The first part of the study investigated the required spectral point-spacing for accurate detection of glucose. This was studied by systematically truncating interferograms before Fourier transforming them to single-beam spectra. A set of training data (70 samples) was collected for multivariate calibration using partial least-squares (PLS) and an external prediction set was used to verify the success of modeling glucose quantitatively. It was found that a relatively large point-spacing (16 cm-1) was successful for prediction of glucose, meaning that a shorter interferogram could be collected. The second part of the study involved collecting interferograms such that the spectral resolution was 16 cm-1 , and investigating methods to extend the usefulness of calibration models for long-term data collection. Near-infrared spectroscopy often suffers from weak signals that are overwhelmed by significant instrumental drift, meaning that calibration models tend to be unsuccessful for data collected several days or months outside the calibration. For updating the calibration models, a set of 50 backgrounds containing only matrix constituents without analyte was collected on each analysis day, and used to Cheatum, Dr. Julie L. P. Jessop, and Dr. Darrell P. Eyman for their academic critiques of this dissertation. I would like to thank my current group members, Yusuf Sulub, Boyong