Light sheet microscopy is a powerful technique for imaging large specimens by taking full advantage of emerging tissue clearing methods. The chemistry behind these techniques has advanced to where we can easily penetrate 1, 5 even 10mm into a specimen with a focused sheet of light. In combination with a macro zoom microscope using high NA large field of view lenses, Cleared Tissue LightSheet can image large field sizes with high resolution in short periods of time.CTLS acquisition is extremely flexible, from ultrafast capture with a 20μm light sheet (left) to high-resolution capture with a 3μm light-sheet shifted 20 times and the resulting 20 sections of best focus tiled to one best-focus image (right).The movie below shows the ventral tegmental nuclear (VTN) group of the mouse cleared with PEGASOS (Jing et al. (2018). Tissue clearing of both hard and soft tissue organs with the PEGASOS method. Cell Research.). Sample courtesy of Dr. Hu Zhao (Texas A&M University).