The presence of metastases to the central nervous system (CNS) is a major challenge in the management of a variety of advanced malignancies. Treatment approaches are often hampered by the priviledged CNS environment, among others established by the highly specific blood–CNS barriers. The role of these barriers has been investigated intensively, but focus has mainly been set on the microvascular blood–brain barrier. In contrast, the role of the blood–cerebrospinal fluid barrier (BCSFB) as entry site for malignant cells into the CNS compartment has been underrecognized for long. In the following, we review recent work on the role of the BCSFB in oncological diseases. In addition to cellular and molecular pathways promoting CNS invasion of tumor cells to form brain metastases, we review the role of the BCSFB and available in vitro models in research on therapeutic aspects, that is, to improve penetration of antineoplastic drugs into the CNS and enhance antitumor immune cell homing to CNS tumor lesions.