In their single-center case-matched analysis of 460 patients with IDH wild-type glioblastoma, Dr. Pallud et al. compared the rates of survival between patients treated, partially treated, or not treated with levetiracetam. The overall survival was longer among patients treated continuously with levetiracetam (median 21 months) when compared with those partially treated (median 16.8 months) and those untreated (median 16.0 months) with levetiracetam (p = 0.027). Furthermore, levetiracetam use was an independent predictor of survival (HR 0.69, 95%CI 0.52–0.93) along with MGMT promoter methylation and gross total tumor resection. A similar effect estimate of levetiracetam use was observed after case matching (n = 54 patients per group, HR 0.63, 95%CI 0.42–0.94). Dr. Mazzucchi and colleagues highlight that seizures have been shown to correlate with progression of low-grade glioma in their experience, and therefore, their prophylaxis with any antiseizure medication may reduce disease progression. However, the efficacy of prophylactic antiseizure medications in patients with glioblastoma has not been confirmed in clinical trials. Whether seizures may lead to glioma progression or may be a biomarker of disease severity remains somewhat controversial. In response, Pallud et al. cite their original work indicating seizures at the time of glioma and glioblastoma diagnosis may be protective. It is possible that seizure at presentation in patients with glial neoplasms may lead to earlier imaging and diagnosis, creating an immortal time bias. Whether prophylactic seizure treatment improves survival in patients with glioblastoma certainly warrants validation in a controlled, clinical trial. Also, the timing of seizure recognition (at diagnosis vs after treatment initiation) may be critical in determining the prognosis for patients diagnosed with glioblastoma.