While the cerebral vascularization develops gradually in two pre- and postnatal waves, the choroid plexuses develop and mature precociously. This confers to the choroid plexus-CSF system a special role in regulating blood-brain exchanges during pre- and early postnatal development. The choroid plexuses fulfill neuroprotective functions that result from the tightness of the choroidal epithelium forming the blood-CSF barrier, from efflux transport systems, and from specific detoxification activities associated to the epithelial cells. The developmental profiles of several of the antioxidant and conjugation enzymes involved in detoxification display a peak of activity centered on the perinatal or early postnatal period, suggesting an adaptation of the choroidal functions to this particularly sensitive period of life. We also provide evidence that the detoxifying function of the blood-CSF barrier can be pharmacologically enhanced through the Nrf2 signaling pathway to better protect the neural fluid environment from drug and toxic accumulation during the neonatal period.