Grade IV gliomas, also known as glioblastoma multiforme (GBM), are incurable, lethal brain tumors, whose average life expectancy is around 15 months. There is a desperate need for a better understanding of the basic biology of these tumors, in order to devise novel, more specific and effective therapeutics. The handling of GBM represents a daunting challenge to clinicians, also considering the few therapeutic options available, none of which can significantly alter the inevitable lethal outcome of these tumors. Hence, the development of effective therapies would greatly benefit from the availability of in vivo GBM models that can reliably mimic the characteristics of malignant cells and the features of the human disease. Candidate new drugs have to be tested in these in vivo models by adopting settings concerning direct intra-brain delivery in order to define their overall therapeutic efficacy under clinical-like conditions. Here, we describe local intracranial delivery of drugs by osmotic mini-pumps.