Publisher Summary This chapter highlights the case of a patient suffering from refractory seizures with hypothalamic hamartoma. The 16-year-old male had a history of seizure onset at the age of 2 years. Initially, the seizures were brief and consisted of staring spells, occurring mainly at night during the transition from waking to sleep. They were refractory to medical treatment and increased in frequency with time. Neuroimaging studies revealed a hypothalamic hamartoma. Medications tried alone or in combination included acetazolamide, carbamazepine, valproate, felbamate, gabapentin, phenytoin, phenobarbital, and lamotrigine. He had been treated with methylphenidate, amoxapine, and thioridazine for behavioral modification. Magnetic resonance imaging of the brain revealed a hypothalamic mass 10–12 mm in diameter from the center of the hypothalamus, consistent with a hypothalamic hamartoma. The patient was initiated on the ketogenic diet and within days showed remarkable improvement. Within 1 year his antiepileptic drugs and the drugs used for behavioral therapy were withdrawn. He tolerates the ketogenic diet wonderfully and has had no complications. His lipid profile is normal. His dysarthria has showed significant improvement. Hypothalamic hamartomas are congenital malformations that consist of masses of neuronal tissue in ectopic locations. They typically originate from one of the mammillary bodies and extend into the interpeduncular cistern.