Chronobiology is the study of the temporal relationships of biological phenomena. All living things evolved in a milieu characterized by constant change based upon the cyclic relationships of the sun, earth and moon. The circadian periodicity is genetically retained by all living organisms. Circadian organization is such a basic property of life that derangements may have lethal consequences. Mammalian circadian rhythms result from a complex organization involving molecular clocks within nearly all “normal” cells and a dedicated neuroanatomical system which coordinates the so-called “peripheral oscillators.” The core of the central clock system is constituted by the su¬prachiasmatic nuclei that are located on the floor of the hy¬pothalamus. This circadian organization is responsible for predictable chang¬es in the tolerability and efficacy of anticancer agents. The circadian rhythm dependent chemotherapy provides indirect evidence for time-dependent variability of the response of the human and murine to anticancer drugs. Doxorubicin, cisplatin, 5-fluorouracil and FUDR have been studied in oral cancer for their circadian pharmacodynamics and toxicology. The outcome of these studies clearly concluded that circadian dependent administration of anticancer drugs reduces drug toxicity and allows substantial increase in the maximally tolerated dose which results in better treatment efficacy and greater comfort for oral cancer patients. Thus chronobiologically modulated chemotherapy hold promising results in treatment of oral cancer and other cancer with increased efficacy and decreased toxicity. In coming years the future of cancer treatment lies in circadian rhythm dependent chemotherapy.