Knowledge on the interaction between circadian rhythm and human epilepsy is relatively poor, although if it exists, this interaction may be of value for better knowledge of pathophysiology and for timing of diagnostic procedures and therapy. It appears that human seizure occurrence may have 24-h rhythmicity, depending on the origin. These findings are endorsed by animal studies. Rats placed in constant darkness showed spontaneous limbic seizures occurring in an endogenously mediated circadian pattern. More studies are available on the influence of epilepsy on circadian rhythms. Significant differences in chronotypes between patients with different epilepsy syndromes have been found and numerous studies have described influences of epilepsy and seizures on sleep. In contrast, knowledge on (core) body temperature and clock genes in patients is minimal. Reduced heart rate variability and changed hormone levels, which are under the influence of the biological clock, have been observed in people with epilepsy. In short, large gaps in the knowledge about the interaction of circadian rhythm and human epilepsy still remain. Proposals for studies in this borderline area between the biological clock and epilepsy will be discussed.