It has been well known for many years that valproic acid (VPA) therapy can induce obesity and important endocrine dysfunctions; among these dysfunctions, the most common are hyperandrogenism, menstrual disorders, polycystic ovary syndrome, hyperinsulinism, and changes in LH, FSH, and sexual and thyroid hormones. Moreover, abnormalities in pubertal development and impaired skeletal growth have been reported. The aim of this review is to analyze the main effects of VPA on endocrinological functions in patients with epilepsy in order to understand in depth the pathophysiological mechanisms and, consequently, to improve the care of these patients.