Any review on adverse effects alone without due reference to the therapeutic benefits of a valuable drug is in danger of exaggerating the side effects. Nevertheless, it is reasonable to expect that some of the signs and symptoms seen in patients with epilepsy may not be due to the epilepsy but rather to the adverse effects of antiepileptic drugs (Schmidt and Seldon, 1982). Awareness of the common and the less well-known adverse effects will increase the safety of a drug, such as valproate, that is taken chronically by many patients worldwide. From a clinical perspective, any unwanted reaction may be seen as an adverse effect. Adverse effects can usually be classified in a small number of rather rare but sometimes fatal and mostly unpredictable drug-induced diseases or in more frequent, mostly mild, dose-related, and reversible side effects (Schmidt, 1983). The adverse effects of valproate are difficult to classify in that scheme, because dose dependency is rare and the mechanisms of most adverse reactions are not well understood. It may therefore be useful to start with an overview of the common adverse effects observed in therapeutic trials, followed by a review of the individual organ systems involved in the adverse effects of valproate, including rather rare drug-induced diseases. The purpose of this review is to provide an overview of the adverse effects of valproate, except for its hepatotoxic and teratogenic actions, which will be covered by Prof. Jeavons (S50–55).