Transcription occurs across more than 70% of the human genome and more than half of currently annotated genes produce functional noncoding RNAs . Of these transcripts, the majority-long, noncoding RNAs (lncRNAs) -are greater than 200 nucleotides in length and are necessary for various roles in the cell . It is increasingly appreciated that these lncRNAs are relevant in both health and disease states, with the brain expressing the largest number of lncRNAs compared to other organs . Glioblastoma (GBM) is an aggressive, fatal brain tumor that demonstrates remarkable intratumoral heterogeneity, which has made the development of effective therapies challenging . The cooperation between genetic and epigenetic alterations drives rapid adaptation that allows therapeutic evasion and recurrence . Given the large repertoire of lncRNAs in normal brain tissue and the well-described roles of lncRNAs in molecular and cellular processes, these transcripts are important to consider in the context of GBM heterogeneity and treatment resistance . Herein, we review the general mechanisms and biological roles of lncRNAs, with a focus on GBM, as well as RNA-based therapeutics currently in development.