Seizures are a common complication of primary (PBT) and metastatic (MBT) brain tumors, affecting approximately 50% of all patients during the course of their illness. Anti-convulsant therapy of these tumor-induced seizures is often inadequate with conventional anti-epileptic drugs (AEDs), due to a variety of factors, including activation of glutaminergic NMDA receptors, immune-mediated neuronal damage, and anatomic alterations of neuronal input pathways. Levetiracetam (LEV) is a new AED with a novel mechanism of action, which includes reducing the Ca++ current through neuron-specific, high voltage activated Ca++ channels (n-type). Because of this unique mechanism, it has been postulated that LEV may be effective in controlling tumor-induced seizures. A retrospective chart review was performed of all patients who had received LEV for seizure control. Forty-one patients were reviewed (22 female, 19 male), with a median age of 47.5 years (range 25-81). There were 34 patients with PBT and 7 with MBT. LEV was used as an add-on AED in 33 patients and as monotherapy in eight patients, with a median dose of 1500 mg/day (range 500-3500). The baseline median seizure frequency for the cohort was 1 per week. After the addition of LEV and follow-up for a minimum of 4 weeks, the median seizure frequency was reduced to 0 per week (59% of patients noted complete seizure control). Overall, the seizure frequency was reduced in 90% of patients (P<0.0001; Sign test). The most common toxicity was somnolence, noted in 37% of patients. LEV was very effective and well tolerated in brain tumor patients with seizures, and should be considered for add-on therapy to current AEDs, or as a substitute anti-convulsant for monotherapy.