The objective of this study is to evaluate the safety and efficacy of vagus nerve stimulation (VNS) in very young children suffering from catastrophic epilepsy and status epilepticus. We reviewed files of 60 VNS-implanted children at our institution and we selected six very young patients, less than 3 years old (mean age at implant 1.6 years). All patients suffered from severe cognitive impairment and catastrophic epilepsy with underlying diagnosis of hemimegalencephaly (1), hypoxic-ischemic encephalopathy (1), tuberous sclerosis complex (1), and malignant migrating partial epilepsy of infancy (3). Three patients were VNS-implanted during admission at intensive care unit (ICU) after developing life-threatening status epilepticus. The mean follow-up time was 41.6 months. The VNS was implanted using a single cervical incision. No surgery-related complications were observed. Four of six children have shown a significant, persistent improvement in seizure control (range, 60–90%). In patients with status, insertion of the vagal nerve stimulator allowed early cessation of status and discharge from ICU. Quality of life and parental satisfaction improved and for three children there was some milestone evolution. Catastrophic epilepsy in infancy can be devastating and difficult to treat with drugs and surgery. If resective surgery is inappropriate or refused, VNS can be considered as a well-tolerated and effective procedure even in toddlers affected by severe epilepsy and multiple developmental disabilities.