We evaluated the clinical responses to add-on therapy with topiramate in eight patients with progressive myoclonic epilepsy (PME). Severe myoclonic seizures disturbing daily activities were persistent despite adequate trials of various combinations of antiepileptic drugs in all patients. After the initiation of topiramate therapy, five patients had a marked decrease in myoclonic seizure frequency, prominent improvement of daily functioning, and recovery from previous drug-related side effects such as weight gain and irregularities of menstruation due to polycystic ovary syndrome. However, we had to discontinue topiramate in three patients because of side effects. Topiramate seems to be a useful alternative agent in the treatment of PME. The antimyoclonic effect provides some independence in daily activities and decreases the side effects related to other antiepileptic drugs, which are clear benefits for this grave disease, although having a short-term effect in some patients.