The endogenous circadian clock modulates cognitive performance over the daily 24-h cycle. Environmental disturbance of the clock, such as shift work or jet lag schedules, compromises sleep, alertness and problem solving. What is not generally appreciated, however, is that the circadian clock also modulates cognitive activity independently of time spent awake. The molecular identification of circadian clock genes in higher eukaryotes has revealed a conserved intracellular mechanism that, if disrupted by mutation, can have significant implications for mental and physical health. These molecular clocks tick away in different brain areas, and their circadian phases and anatomical relationships to the central brain pacemakers indicate new ways for understanding the mechanisms of interaction between circadian clocks, sleep and cognition.