In the present review, first we present the anatomical connections used by the mammalian biological clock to enforce its endogenous rhythmicity on the rest of the body, especially the energy homeostatic systems. Subsequently, we present a number of physiological experiments investigating the functional significance of this neuroanatomical substrate. Together, this overview of experimental data, for a major part derived from our own experiments, reveals a highly specialized organization of connections between the endogenous pacemaker and both the presympathetic and pre-parasympathetic hypothalamic systems, providing the biological clock with a unique opportunity to modulate the balance of sympathetic/parasympathetic inputs to peripheral organs. We hypothesize that a well-balanced autonomic nervous input, differentiated according to the time of day and the body compartment, is an important companion to withstand the progressive burden of the current 24/7 society on our health and well-being.