During brain inflammation, rigorous regulation of brain-body communication is required for sufficient, but not excessive, immune activation. As a crucial neuroimmune interface, the choroid plexus (ChP) epithelium serves as both a physical barrier between blood and cerebrospinal fluid (CSF) and a gateway allowing peripheral immune cell entry into the central nervous system (CNS). Recent years have witnessed increasing investigations of ChP events during brain inflammation. Here, we contextualize new findings with established ChP core functions, including CSF secretion and blood-CSF barrier regulation. We reason that the ChP is an organ where immune and nonimmune cells collaborate to defend the CNS. We discuss the pertinent mechanisms and the implications for neurologic disease etiology and treatment. Finally, we discuss outstanding questions for this rapidly expanding field and suggest key technologies and experimental steps to elucidate the full range of ChP functions during neuroinflammatory conditions, such as infection, injury, and aging.