High resolution episcopic microscopy (HREM) is an ex vivo, optical block face scanning method. Specimens, with a volume of up to 10 x 10 x 15 mm3 are harvested, dehydrated and embedded in methacrylate resin. Then they are mounted and physically sectioned on an HREM apparatus. During sectioning, images of each fresh block surface are captured in an automated way, while the physical sections are usually discarded – although it is possible to collect and mount them for later histopathological analysis. The images are of near histological quality and permit identification of cells and small structures in their natural surrounding and tissue context. Typical series of HREM images consist of a few hundred to several thousand sections, which are produced in a few hours. Since they are inherently aligned, they are immediately virtually stacked and converted to 3D data volumes with typical voxel sizes of 1x1x1 µm3 to 6x6x6 µm3. This imaging technology has been applied for structural and morphometric analyses of the 3D architecture and morphology of a wide range of materials, including tissues and organs of humans, biomedical model animals, skin substitutes, paper and plants.