Until we turned our nights into days and began to travel in aircraft across multiple time zones, we were largely unaware that we possess a 'day within' driven by an internal body clock. Yet the striking impairment of our abilities in the early hours of the morning soon reminds us that we are slaves to our biology. Our ability to perform mathematical calculations or other intellectual tasks between 04.00 and 06.00 h is worse than if we had consumed several shots of whisky and would be classified as legally drunk. Biological clocks drive or alter our sleep patterns, alertness, mood, physical strength, blood pressure and every other aspect of our physiology and behaviour. Our emerging understanding of how these 24 h rhythms are generated and regulated is not only one of the great success stories of modern biology, but is also informing many areas of human health. Sleep and circadian rhythm disruption (SCRD) is a feature shared by some of the most challenging diseases of our time, including neuropsychiatric illness and serious disorders of the eye. Sleep and circadian rhythm disruption is also commonly seen across many sectors of society, from teenagers to shift workers. We also now appreciate that SCRD is far more than feeling sleepy at an inappropriate time. It promotes multiple illnesses ranging across abnormal metabolism, heart disease, reduced immunity, increased stress and abnormal cognition and mood states. This short review considers how 24 h rhythms are generated and regulated, the consequences of working against our body clock and the emerging relationship between SCRD and mental illness.