Increasing number of studies shows significant reductions in bone mineral density in patients with epilepsy treated with enzyme-inducing anti-seizure medications (EIASM), valproic acid, and newer anti-seizure medications (ASM). ASM seems to be a specific risk factor for the development of osteoporosis affecting 11%–31% of patients with epilepsy and leads to 2 to 6 times increased risk of fractures compared to the background population. Treatment with ASM clearly contributes to epilepsy-associated bone disease. Yet, the exact pathophysiological mechanism has not been established; however, several hypotheses were suggested, especially in relation to EIASM. As the long-lasting medical treatment, often in polytherapy, has shown negative effects on bone health, it indicates the need for guidelines for the prevention and management of bone disease to be included in the follow-up of patients with epilepsy. An algorithm for following bone status during the treatment has been suggested based on Danish national guidelines.