With advances in genomic profiling and sequencing technology, we are beginning to understand the landscape of the genetic events that accumulated during the neoplastic process. The insights gleamed from these genomic profiling studies with regards to glioblastoma etiology has been particularly satisfying because it cemented the clinical pertinence of major concepts in cancer biology- concepts developed over the past three decades. This article will review how the glioblastoma genomic data set serves as an illustrative platform for the concepts put forward by Hanahan and Weinberg on the cancer phenotype. The picture emerging suggests that most glioblastomas evolve along a multitude of pathways rather than a single defined pathway. In this context, the article will further provide a discussion of the subtypes of glioblastoma as they relate to key principles of developmental neurobiology.