Glioblastoma multiforme (GBM) is one of the most common and most malignant of the brain tumors. Gliomas can be classified into four different grades according to their histologic characteristics; the most aggressive of the gliomas is glioblastoma multiforme (grade IV). Despite optimal treatment, the median survival is only 12 to 15 months. In the past few years, important advances were made in understanding the biology and pathology of malignant gliomas. A mouse model of brain tumors using inducible lentiviral vectors is described here. In this approach, a lenti-vector with loxP sites flanking the gene of interest (oncogene) is injected into mice expressing Cre recombinase under the control of a brain-specific promoter. The steps to perform cell-type/region-specific injection of Cre-loxP-controlled lentiviral vectors in the brain of adult mice are described here in detail. Curr. Protoc. Mouse Biol. 3:121-139 © 2013 by John Wiley & Sons, Inc.