In terms of pharmacology, drug delivery is an important obstacle in the development of brain tumor chemotherapy. The blood-brain barrier limits the drug penetration in normal brain tissue around the tumor and at distant potential metastatic sites. In the tumor, the altered blood-brain barrier, ie blood-tumor barrier, decreases the drug entry in malignant cells. The knowledge of the blood-brain barrier physiology and the definition of the laws that govern the drug delivery to the central nervous system allow the development of new strategies to increase drug delivery to the tumor. In pediatric oncology, the more appropriate methods are the use of anticancer agents that easily cross the blood-brain barrier and the development of high-dose systemic chemotherapy regimens with or without bone marrow rescue.