Patients with glioblastoma are among the cancer patients with the highest risk of developing venous thromboembolism (VTE). Long-term thromboprophylaxis is not generally prescribed because of the increased susceptibility of glioblastoma patients to intracranial hemorrhage. This review provides an overview of the current clinical standard for glioblastoma patients, as well as the molecular and genetic background which underlies the high incidence of VTE. The two main procoagulant proteins involved in glioblastoma-related VTE, podoplanin and tissue factor, are described, in addition to the genetic aberrations that can be linked to a hypercoagulable state in glioblastoma. Furthermore, possible novel biomarkers and future treatment strategies are discussed, along with the potential of sequencing approaches toward personalized risk prediction for VTE. A glioblastoma-specific VTE risk stratification model may help identifying those patients in which the increased risk of bleeding due to extended anticoagulation is outweighed by the decreased risk of VTE.