The involvement of glia in the development and progression of a wide spectrum of neurodegenerative diseases has become a key focus in translational neuroscience research. To improve the chance of translation from the lab to the clinic, we need models that capture the complexity, heterogeneity and architecture of the adult human brain. Living human brain slice cultures are ideal for the study of glia as they maintain 3D micro-circuit organisation and mixed cellular populations. Our lab specialises in the use of live human cortical tissue to study neurodegenerative disorders, and the involvement of glia. Human brain slice cultures (HBSCs) are generated from surplus neocortical access tissue, taken from consenting patients undergoing tumour debulking surgery.  Tissue samples are maintained in ice-cold aCSF, mounted in agar and sliced to 300um, before being plated onto semi-permeable PVDF membranes according to an interface protocol adapted from more common murine models. Optimisation of this culturing protocol has enabled the study of glia in a variety of ways. We have shown that we can observe living human astrocytes and microglia for multiple weeks in culture. Astrocytes can be readily transduced with AAVs for live imaging and RNA knockdown, providing an ideal system to study these cells in a variety of contexts and probe mechanistic pathways. Our lab has utilised such methods to quantify the degree of synaptic engulfment by astrocytes and microglia in response to various experimental insults. We have also shown that they produce a strong neuroinflammatory response when exposed to LPS, indicating the despite their resection and proximity to tumours, the tissue’s neuroinflammatory output is not maximised. Together, our model bridges a gap between murine and human post-mortem study, with the aim of increasing the likelihood of success when translating glial mechanisms of disease.