The key for researching the mechanisms underlying pre- and postnatal development and growth, as well as pathologies, tissue regeneration, and therapeutic success, is multidimensional imaging of the formation, regeneration, and remodeling of organs and tissues. While numerous cutting-edge techniques permit three-dimensional (3D) and four-dimensional (4D) visualization of the organ morphology, topology, and function on the one hand, and of cellular and subcellular structures and processes on the other hand, only a few methods exist that permit 3D visualization of tissue morphology and architecture at a mesoscopic level. This chapter introduces high-resolution episcopic microscopy (HREM) as a method for visualizing the architecture of complex anatomic structures and tissues at a voxel resolution of 1 μm3 and bigger and volumes of 4 cm3 and smaller. HREM is a technique that creates digital volume data from histologically processed and physically sectioned organic specimens, including embryos and biopsy material from biomedical models and humans. Two examples of its usefulness to study organ and tissue remodeling as case studies are given. The first studies vascular remodeling in embryogenesis, visualizing blood vessels in embryos of several developmental stages; the second studies the tissue composition and architecture of skin substitutes and skin biopsies, harvested from normal and regenerating skin. Both case studies do not present new data, but sum up already published works, which demonstrate the capacity of HREM to assist biomedical research and regenerative medicine.