Abstract: Electron microscopy (EM) provides a unique ability to visualize structural detail with a resolution orders of magnitude better than other imaging techniques. Applied conventionally, its limitation is that each acquired image represents a small area with a section thickness significantly less than 100 nm. Recently, techniques have been developed that allow thousands of relatively large serial-sections to be collected and efficiently imaged at full EM resolution, with the images then being stitched back together to produce a 3D volume.  Within such a volume, every subcellular structure or cellular connection can be identified and mapped, i.e. connectomics. These methods offer the opportunity of revealing a comprehensive view of large volumes of neural tissue. With the increasing use of automated technologies, it is now possible to use large-scale serial-section electron microscopy to generate reconstructions of various brain regions with a resolution of 4 nm or better (Kasthuri et al., 2015; Baena et al., 2019). At this resolution, excitatory and inhibitory chemical synapses can be seen; the existence of electrical synapses (gap junctions), the presence of neuromodulatory peptides and biogenic amines, and the identification of local microcircuits can all be observed (Swanson and Lichtman, 2016).  Furthermore, relationships with various types of glial cells are readily seen, and cells associated with vascular elements and non-neuronal/glial cell types can be distinguished.  Further, the fine structure of organelles, including mitochondria, endoplasmic reticulum, lysosomes, and autophagosomes, along with cytoskeletal elements are within the resolution of these techniques. Thus, a continuum of scale, from sub-organelle structure, through the cellular level, up to a wide field tissue perspective can be viewed and analyzed simultaneously.  Such techniques have been used to map nerve regeneration in 3D (Leckenby et al., 2019), to investigate developmental rewiring in the cerebellum (Wilson et al., 2019); to explore the network connectivity in visual thalamus (Morgan and Lichtman, 2020), and to define the neuronal connectivity and relationships with glial cells in the human fovea (Dacey et al., 2017; Packer et al., 2017).