Ongoing refinements in pharmacology continue to provide new medications for the treatment of seizure disorders and other neurologic conditions. The authors present the cases of two children who developed relatively uncommon adverse effects to new anticonvulsant medications, including metabolic acidosis with topiramate and hyponatremia with oxcarbazepine. In one of our two patients, intraoperative acidosis related to topiramate was noted. Appropriate investigation with documentation of normal serum lactate resulted in the exclusion of other potentially serious causes of acidosis and in the identification of topiramate as the causative agent. In our second patient, hyponatremia and status epilepticus resulted from therapy with oxcarbazepine. Prompt recognition of hyponatremia, fluid restriction, and cessation of oxcarbazepine therapy resulted in prompt correction of the hyponatremia. We review previous reports of these adverse effects with topiramate and oxcarbazepine, describe the pathophysiology of these metabolic alterations, provide treatment strategies, and make suggestions for monitoring patients during therapy with these anticonvulsant medications.