History of discovery of sodium valproate and its clinical application is briefly described in this chapter. Now sodium valproate is used in the treatment of epilepsy in children and adults and prevention of epilepsy after brain surgery. Also, valproate is used as mood stabilizer in bipolar disorder in psychiatry and treatment of migraine. Valproate is very useful drug for epilepsy and the use is spreading rapidly; however, soon after its launch, valproate-induced hepatotoxicity (VHT) and valproate-induced hyperammonemic encephalopathy (VHE) were reported. Various studies were reported about the etiology and characteristics of high-risk population of VHT and VHE. Then, it appeared that carnitine deficiency is closely related to VHT or VHE and effects of carnitine supplementation therapy were reported. After recognition of risk factors, the occurrence of VHT drastically decreased. Valproate administration causes hyperammonemia at a very high rate but most of them are asymptomatic. There are controversy about carnitine supplementation in these populations, but ammonia toxicity in children is very dangerous for brain development. In the case of valproate intoxication, intravenous carnitine supplementation is very useful. In this chapter, these clinical research, recommendation, case reports in neurology, psychiatry, and emergency are introduced and reviewed in detail.