The discovery just a few years ago that only a few days of partial sleep restriction, in otherwise healthy young men, can induce changes in glucose regulation that are indicative of a trajectory toward insulin resistance and diabetes, introduced a new era of sleep medicine and a new found interest in sleep and metabolism. Indeed, there is now considerable evidence from experimental and epidemiological studies that sleep loss and obesity are “interacting epidemics”. Similarly, the recent discovery that mice carrying a mutation in a canonical circadian clock gene show alterations not just in the timing of sleep and wake, but also in the amount of sleep and sleep architecture, as well as changes in metabolism, has opened up a new era for thinking about how the circadian clock, sleep-wake and energy regulatory systems are integrated at the molecular, genetic and behavioral levels. Further support for the integration of these systems at many levels comes from studies showing that genetic and environmentally induced changes in metabolism can influence sleep and circadian rhythms. The fact that the core molecular circadian clock machinery is found in most of the cells and tissues of the CNS and periphery and regulates the diurnal timing of expression of hundreds of “clock controlled genes”, and that core molecular circadian genes and proteins are also part of key energy metabolic pathways, has opened up new frontiers for investigating the importance of rhythmicity for mental and physical health. These lines of research are only in their infancy, but nevertheless, have provided a conceptual and experimental framework that potentially has great importance for developing a deeper understanding of complex behavioral and physiological processes. This lecture will review this new and rapidly evolving frontier of neuroscience.