Topiramate has been shown to be highly effective for preventive treatment of migraine and its use has been significantly increased in the last few years. However, around 10% of migraineurs develop a worsening of their symptoms while on topiramate. We report a 33-year-old woman with familial hemiplegic migraine (FHM) who experienced worsening of her symptoms following repeated topiramate intake. Withdrawal of the drug rapidly constantly induced resolution of the symptoms. This is the first report of topiramate-associated worsening symptoms in FHM. It is important to be aware of this phenomenon, as topiramate is worldwide-used drug for migraine treatment.