It has long been appreciated that the brain represents a pharmacological sanctuary and is selectively “protected” from the toxic effects of many chemotherapeutic agents. These include vincristine and doxorubicin (aka adriamycin), which fail to penetrate the blood–brain barrier as well as their lipid solubilities would suggest [162]. A major part of this failure to penetrate has since been attributed to the presence of the multidrug transporter, P-glycoprotein. Absence of this transporter in knock-out mice was shown to allow entry of toxic agents including ivermectin [203]. P-glycoprotein was found to be located in the luminal membrane (see e.g. [204–209]) of the endothelial cells and is believed to act there to transport substrates out of the cells so rapidly that little remains to penetrate the abluminal membrane and enter the brain.