Circadian rhythms permeate mammalian biology. They are manifested in the temporal organisation of behavioural, physiological, cellular and neuronal processes. Whereas it has been shown recently that these ∼24-hour cycles are intrinsic to the cell and persist in vitro, internal synchrony in mammals is largely governed by the hypothalamic suprachiasmatic nuclei that facilitate anticipation of, and adaptation to, the solar cycle. Our timekeeping mechanism is deeply embedded in cell function and is modelled as a network of transcriptional and/or post-translational feedback loops. Concurrent with this, we are beginning to understand how this ancient timekeeper interacts with myriad cell systems, including signal transduction cascades and the cell cycle, and thus impacts on disease. An exemplary area where this knowledge is rapidly expanding and contributing to novel therapies is cancer, where the Period genes have been identified as tumour suppressors. In more complex disorders, where aetiology remains controversial, interactions with the clockwork are only now starting to be appreciated.