The syndrome of malignant migrating partial seizures of infancy (MMPEI) is characterized by early onset of multiple seizures types, highly pharmaco-resistant seizures, and overall poor prognosis. In this study, we investigated retrospectively the efficacy of rufinamide (RUF) in five infants with MMPEI, by examining seizure type and frequency, EEG features and antiepileptic drug use. The data demonstrate that two of the five patients showed good efficacy and tolerability for RUF with a > 50% reduction in seizure frequency. The use of RUF for the treatment of MMPEI may therefore provide some hope for such infants and should be further validated. [Published with video sequences].