Traditional histology relies on thin sections of small samples for studying human tissues, which limits our understanding of the complex structure and anatomical relationships of whole organs. Gross anatomy and medical imaging on the other hand lack the resolution and specificity to visualize histological structures. Tissue clearing methods are emerging as innovative solutions to transcend this constraint by revealing the spatial architecture of large tissues samples. However, making adult human organs transparent remains a challenge, given their size, density and endogenous fluorescence. We have developed and adapted novel techniques for clearing and labeling efficiently postmortem human organs, showing their compatibility with different organs and tissue types. Combined with light-sheet microscopy and advanced image-processing tools, we have reconstructed their cellular architecture, innervation and vascularization in three dimensions. Whole-organ tissue imaging enables a multimodal approach for the study of structure-function relationship in human anatomy.