Abstract: Disclosed herein are systems and methods for performing angled confocal spectroscopy. Angled confocal spectroscopy permits sensitive, non-invasive investigation of numerous analytes in a wide variety of samples, including tissues and bodily fluids. The methods and systems disclosed herein can be used to measure spectroscopic signatures of analytes within well-defined and very small regions of samples, while at the same time achieving superior rejection of signal contributions from analytes within the sample that do not fall within a volume of interest. Accordingly, measurements can be performed at comparatively high signal-to-noise ratios, and can provide information such as concentrations and distributions of sample analytes at high spatial resolution. By using cylindrically-focused illumination light, samples can be excited by a “sheet” of light, allowing spatial signal averaging and enhancing the stability and reproducibility of the measurements.