In dairy cows, overfeeding during the dry period leads to overcondition at calving and to depression of appetite after calving. As a consequence, at calving overconditioned high‐producing dairy cows inevitably go into a more severe negative energy balance (NEB) postpartum than cows that have a normal appetite. During the period of NEB, the energy requirements of the cow are satisfied by lipolysis and proteolysis. Lipolysis results in an increased concentration of non esterified fatty acids (NEFA) in the blood. In the liver, these NEFA are predominantly esterified to triacylglycerols (TAG) that are secreted in very low density lipoproteins (VLDL). In early lactation in cows with a severe NEB, the capacity of the liver to maintain the export of the TAG in the form of VLDL in balance with the hepatic TAG production is not always adequate. As a result, the excess amount of TAG accumulates in the liver, leading to fatty infiltration of the liver (hepatic lipidosis or fatty liver). The NEB and/or fatty liver postpartum are frequently associated with postparturient problems. In general, a severe NEB induces changes in biochemical, endocrinological, and metabolic pathways that are responsible for production, maintenance of health, and reproduction of the postparturient dairy cow. These changes include a decrease in blood glucose and insulin concentrations, and an increase in blood NEFA concentrations. High NEFA concentrations caused by intensive lipolysis are accompanied by impairment of the immune system, making the cows more vulnerable to infections. Metabolic diseases such as ketosis, milk fever, and displaced abomasum are related to overcondition at calving. The changes in biochemical, endocrinological, and metabolic pathways are associated with delay of the first visible signs of oestrus, an increase in the interval from calving to first ovulation, a decrease in conception rate, and a prolonged calving interval. It is possible that the increased blood NEFA concentration directly impairs ovarian function.