Primary brain tumors, particularly glioblastomas, remain a challenge for oncology. Uncontrolled cellular proliferation, lack of apoptosis, invasion, and angiogenesis are among the biologic processes that render these tumors both aggressive and difficult to treat. An understanding of the genetics and molecular events regulating these aggressive tumors is beginning to emerge, partly because of recent knowledge in genomics, gene expression analysis, and mouse tumor models. As a result, it is now generally accepted that brain tumors, particularly those arising from cells of glial lineage, result from stepwise accumulation of deleterious genetic alterations. Several genetic abnormalities have been described, and current research is aimed at elucidating their causal association with brain tumor formation and progression. The purpose of this review is to summarize some of the most important recently published findings on the molecular genetics of primary gliomas.