Recent years have witnessed rapid developments of high-resolution optical imaging technologies, including (but not limited to) confocal, multispectral, optical coherence tomography, multiphoton fluorescence, second harmonic generation, Raman and/or coherent anti-Stokes Raman spectroscopy, and stimulated Raman scattering microscopy. The high-resolution, noninvasive (or minimally invasive), and real-time imaging capability make these technologies well positioned for performing “optical biopsy” in situ and in real time, with a resolution approaching or at that of standard histology. Clinical translation of these technologies, particularly for assessing internal organs, requires miniature probes for delivery, scanning, and collection of the probing/imaging beams. Endomicroscopy is emerging as a field to fulfil this need and represents tremendous potential for improving the current diagnostic yields. Advances in fiber optics, micro-optics, miniature light sources, sensitive detectors, and MEMS technologies have yielded extremely compact, highly flexible systems which easily interface with current endoscopes. Endomicroscopy can be combined with other “red-flagging” clinical diagnostic instruments to enable surveillance over a large area and confirm optimal sites for biopsy in a small area during a procedure.