We all have embedded within our biology a body clock or “circadian system”. The circadian system is used to anticipate the 24 hour day/night cycle so that physiology and behavior can be fine-tuned and adapted to the varying demands of activity and rest. In anticipation of wake, while we are still asleep, body temperature, metabolism and alertness begin to rise in preparation for the activity ahead. And in the same way, in anticipation of sleep, the body begins to slow-down, blood pressure drops, alertness falls and core body temperature declines. The internal clock driving these daily rhythms is not exactly 24 hours, in most of us it is a little longer. As a result, to keep the entire circadian system synchronized, the body clock is adjusted on a daily basis by the changes in light intensity around dawn and dusk. Without this daily re-setting of the clock, 24 hour body rhythms of sleep and wake would rapidly become desynchronized with the real world and lose their adaptive value. The master clock is located within the base of the brain in a small paired structure called the suprachiasmatic nuclei – abbreviated to the SCN. The SCN are located just above where the optic nerves enter the brain and they contain around 50,000 cells, all of which contain their own individual molecular clock. The SCN cells work together to generate a near 24 signal throughout the body. Small changes in the genes that generate the molecular clock have been associated with the tendency to be a “morning” or “evening” person. Until recently, It was thought that only the SCN contains clock cells, but we now know that all cells of the body contain their own molecular clock. As a result the SCN coordinates the 24h rhythmic activity of billions and billions of cells throughout the body. The SCN receives a direct projection from the eye which adjusts all the cells in the SCN to the light/dark cycle. In addition to the rod and cone photoreceptors of the eye which provide us with our sense of vision, the eye contains a recently discovered 3rd class of light-sensitive cell called a “photosensitive retinal ganglion cell”. There are relatively few of these cells within the eye but they are critical for the measurement of environmental brightness, and hence adjustment of the SCN to dawn and dusk. In parallel with our increased understanding of the neuroscience of circadian rhythms, there is a growing appreciation of the severe consequences of ignoring the impact of these rhythms on diverse areas our health and quality of life. For example, the discovery of the pRGCs within the eye has transformed our understanding of blindness. We now appreciate that eye diseases which result in rod and cone photoreceptor death need not result in the loss of pRGC light detection. In these cases if a visually blind individual retains pRGC function they should be encouraged to expose their eyes to sufficient day-time light to maintain normal circadian regulation and sleep-wake timing. Even without sight, these eyes should be preserved at all costs as their loss will plunge an individual into a world without any sense of time; Additionally, individuals with eye diseases of the inner retina, which result in retinal ganglion cell death (e.g. glaucoma), are at particular risk of circadian rhythm disruption. Such individuals would be strong candidates for treatment with appropriately timed medications that help consolidate sleep timing. Until recently, sleep and circadian rhythms have rarely been addressed in clinical departments of ophthalmology, yet worldwide there are over 50 million people classified as blind and perhaps a further 300 million with severe visual loss. The quality of life and health of many of these individuals would be improved if there were a greater understanding by ophthalmologists of how the eye regulates our internal time. Jet-lag represents another example where the circadian system becomes uncoupled from the environment, but in this case because of travel across multiple time-zones. Upon exposure to the new light/dark cycle it takes the circadian system days to readjust to local time. Furthermore, the timing of the multiple cellular clocks throughout the body becomes uncoupled for variable periods of time before adjustment. The net result is a body that is poorly adapted to function in the new time-zone. Insomnia, fatigue, impaired cognition, depression, metabolic and gastrointestinal problems all persist until the circadian system has adapted fully to the new light/dark cycle. The number of people affected by jet-lag is rising rapidly, but little is done to address the problems suffered by these individuals. This presentation will consider the remarkable discoveries of how our circadian rhythms are generated and regulated by light. The second part of the talk will consider how a knowledge of this physiology is having a major impact upon both medicine and in the way we structure and our society.