Tissue clearing in combination with light sheet microscopy is now used widely since we introduced it 15 years ago for the study of mouse brains. However the application of this technology to elucidate the structure of human tissues has proved much more challenging. The use of endogenous fluorescent marker is not possible in humans and staining with antibodies is difficult due to diffusion problems. In addition the standard diffusion based clearing protocols take weeks to months to clear human tissue. Notoriously difficult is clearing of tumors due to their high cell density. We therefore developed in the last years a new clearing, pathoDISCO, which allows clearing of tumor tissue in the centimeter range within days. We were able to specifically stain cytoplasm, cell nuclei, collagen and blood vessels in breast cancer and Glioblastoma specimens. In 3D recording also the important aspect of neovascularisation and vessel tortuosity can be quantified and may be used in future as predictive marker in many cancers. In the last years we developed our clearing technology further to investigate larger parts of the human brain. We could clear a whole human hippocampus and cerebellum visualizing different neuronal layers by the autofluorescence of lipofuscins. For the visualization of axons we are developing a novel chemical and optical approach allowing the visualization of refractive index differences of myelinated axons. This technology should open the way to study the human connectome in 3D and at high resolution.