Especially during growth, puberty, and menopause, profound changes including maturation of the growth hormone, sex steroid, and thyroid axes, as well as alterations in lipid homeostasis, cardiac integrity, and other enzyme systems, occur physiologically. With epilepsy, however, things are often changing, and there may be a complicated interplay between hormones, epilepsy, and antiepileptic drugs (AEDs). On the one hand, epilepsy itself possibly elicits diverse effects on different enzyme systems including sex steroids, the neuro-cardio-endocrine axis, and bone health. On the other hand, different AEDs are known to induce neuroendocrine changes (e.g., lipid metabolism) that may have deleterious consequences on health and well-being later in life. It is important for physicians and epileptologists to have in mind and to consider the endocrine effects induced by epilepsy itself or by a certain AED when starting antiepileptic therapy, especially when it is expected that long-term treatment will be necessary.