The transition period of the dairy cow involves the end of pregnancy, parturition, and the onset of lactation. Multifaceted and rapid changes occur during this time, and in particular, the increase of milk secretion requires the large-scale reorientation of metabolism. The underlying mechanisms of this metabolic regulation are collectively named homeorhesis, a process that governs milk production during this phase and that exhibits (A) a chronic nature, (B) the simultaneous inclusion of multiple tissues, and (C) altered responses to homeostatic signals, but (D) no direct feedback mechanisms for possible control or limitation. Priority of milk production is one important consequence of this homeorhetic regulation with possible constraints on other physiological functions. These general properties of the homeorhetic regulation of milk secretion are specifically characterized by a) milk production according milking (suckling) frequency, b) a natural but inadequate dry matter intake, c) the mobilization of fat acids + glycerol from adipose tissue and of amino acids from protein, d) the partitioning of metabolites, IgG, and dietary nutrients to the mammary gland, e) the stimulation of milk production by high protein intake, and f) a negligible negative energy balance (NEB) at low milk production. Such a combination assures the optimal milk yield for the nutrition of the calf and for its successful survival but without a metabolic challenge or health risk for the cow. However, selection for higher milk production (uncoupled from calf nutrition) and management have changed the above-listed properties, and the regulation of homeorhetic milk production of the modern high-producing dairy cow is nowadays mostly characterized by a) increasing and maximal milk production at increased milking frequency and, under certain circumstances, the uncoupling of the GH-IGF-1 axis, b) enduring insufficient dry matter intake in relation to requirement, c) the mobilization of energy (lipolysis) and release of non-esterified fatty acids (NEFA) above the acute requirement, d) the mobilization of amino acids, e) the partitioning of metabolites, IgG, and dietary nutrient to the mammary gland, f) the potential enhanced partitioning of energy to the mammary gland at high CP intake, g) a sudden and long-lasting NEB, and h) possibly lower weight gain or even net loss of energy during the entire lactation period. These altered and often unfavorable characteristics of high milk production are, furthermore, still regulated by homeorhesis and are thus also given top priority, lack feedback control, and possibly ensue at the expense of other functions without regard for health risks. Hence, the promotion of milk yield by breeding or management might cause metabolic overload, imbalances, or even antagonisms and makes possible health hazards evident. The high incidence of various diseases, the untimely culling rates, and the increasing number of dead cows during early lactation support the assumption of general health threats at high milk production. For this reason, more attention should be paid to the physiological mechanisms of homeorhetic-regulated milk production, its indisputable alterations by breeding and management, and the resulting health risks.