<b><i>Background:</i></b> Phenobarbitone (PB) is the first-line anti-convulsant for neonatal seizures. The use of peritoneal dialysis (PD) to enhance drug elimination in cases of neonatal PB overdose has not been reported. <b><i>Objective:</i></b> To report a case of neonatal severe PB toxicity and review the elimination of PB by PD. <b><i>Methods:</i></b> Assessment of PD drug clearance. <b><i>Results:</i></b> A neonate with prolonged seizures was administered PB. Encephalopathy and myocardial failure developed, which were initially suspected to be secondary to hypoxia. At 42 h of age, the serum PB concentration was in the toxic range at 131 mg/L. Despite supportive care, the infant's condition deteriorated with escalating inotropes and the need for CPR. Enhanced PB elimination via multiple-dose activated charcoal and exchange transfusion were considered too risky. Hourly PD cycles via Tenckhoff catheter were commenced, based on reports suggesting that PD enhances PB clearance. The clinical state of the infant then improved. PD administration was continued for 60 h, recovering 20% of the estimated total PB body load. The infant survived and there were no PD complications. <b><i>Conclusions:</i></b> PD increased PB clearance in this neonate, correlating with clinical recovery. Where other techniques are not possible, PD may have a role to play in enhancing PB elimination.