Arboviruses are transmitted by arthropods, and their spread from endemic to nonendemic regions has been accelerated by deforestation, climate change, and global mobility. Arbovirus infection in human results in symptoms ranging from mild to life threatening, with the impairment of central nervous system functions being reported in severe cases. Despite its clinical relevance, the mechanisms by which arboviruses led to neural dysfunction are still poorly understood. The lack of a widespread human central nervous system model to study the virus–host interaction challenges the advance of our knowledge on these mechanisms. In this context, human brain-derived ex vivo models have the advantage of preserving cellular diversity, cell connections, and tissue cytoarchitecture found in human brain, raising them as a powerful strategy to elucidate the cellular- molecular alterations underlying brain diseases. Here, we review recent advances in the field of neurotropic arboviruses obtained using ex vivo human brain tissue as the experimental model.