AbstractGlioblastoma is a highly heterogeneous tumor whose pathophysiological complexities dictate both the diagnosis of disease severity as well as response to therapy. Conventional diagnostic tools and standard treatment regimens have only managed to achieve limited success in the management of patients suspected of glioblastoma. Extracellular vesicles are an emerging liquid biopsy tool that has shown great promise in resolving the limitations presented by the heterogeneous nature of glioblastoma. Here we discuss the contrasting yet interdependent dual role of extracellular vesicles as communication agents that contribute to the progression of glioblastoma by creating a heterogeneous microenvironment and as a liquid biopsy tool providing an opportunity to accurately identify the disease severity and progression.