The choroid plexus (ChP) envelops the brain ventricular system and is considered the source of cerebrospinal fluid (CSF). It is a unique interface known as the blood-CSF barrier that is poised among the central nervous system (CNS), circulation, and immune system, providing a spectrum of functions essential to the brain’s homeostasis. The ChP epithelial cells are ciliated and constantly generate CSF, which circulates in the whole CNS and functionally connects ChP with all other brain structures. Human choroid plexus organoids (ChPOs) from pluripotent stem cells have both functional epithelial barrier and CSF-like secretion properties, which resemble human ChP development and recapitulate its dysfunctions in many neurological disorders. Recently, the ChPOs have continued to evolve into a more complex system by incorporating immune cells such as microglia, faithfully representing their immune competency and antiviral functions. Here, we summarize recent advances in the development of ChPO methodologies and discuss their applications in modeling human brain development and related CNS diseases. In addition, we introduce the newest microglia-containing ChPO system and highlight its applications in modeling neurological disorders.