Fourier transform infrared spectroscopy (FTIR) reveals biochemical 'fingerprints' and has found disease patterns in excised human tissues. Fiber-optic probes have been developed for FTIR in living systems, allowing for cancer detection. There are challenges to making in vivo FTIR a reality, which are being addressed through hardware advances, determining key wavelengths and tissue preparation. Fiber-optic evanescent wave spectroscopy (FEWS)-FTIR with endoscope-compatible fiber-optic silver halide probes is feasible, and could prove useful for distinguishing premalignant and malignant tissues from biopsies or within patients. Developments of smaller silver halide probes as well as in vivo tissue drying methods will move this approach closer to the clinic where it can be used for early cancer detection, disease characterization and guided biopsies.