Tissue spectroscopy for gastrointestinal diseases has made rapid strides in methodology and technology, with recent studies showing very promising results for the detection of pre-cancers and cancers. Laser-induced fluorescence spectroscopy, elastic scattering spectroscopy, and Raman spectroscopy have all shown favorable results in the diagnosis of malignancies and dysplasia in a number of small studies, both in vitro and in vivo. While technical limitations have been encountered with each of the techniques, significant advances have been made in the last year that may allow a highly sensitive and specific diagnosis to be generated within seconds, allowing directed or guided biopsies or therapy during a single procedure. Large multicenter trials will be necessary to demonstrate the efficacy, usefulness, and efficiency of these new tools.