Breakthrough seizure activity has been reported with conversion from brand name to generic anticonvulsants. This has prompted several organizations to support physician notification of generic substitution and patient consent. Recently, a generic formulation of levetiracetam has become available. Risk of seizures with generic levetiracetam has yet to be reported. Literature was reviewed regarding risk of generic substitution. Four cases of seizure activity in primary brain tumor patients after conversion from Keppra to generic levetiracetam are reported. In all cases, there was no evidence of tumor growth or concurrent illness that would increase the risk of seizures. In three cases, the patients have remained seizure free with conversion back to Keppra. The final patient required an increased dose of levetiracetam. As has been described with generic substitution of other anticonvulsants, patients switched to generic levetiracetam may be at risk for breakthrough seizure activity.