Caffeine is the most widely consumed psychostimulant drug in the world. With intermittent exposures, caffeine may act as a mild analgesic for headache or as an adjuvant for the actions of other analgesics. Chronic repetitive exposures to caffeine increase the risks for development of analgesic-overuse headache, chronic daily headache, and physical dependency. Cessation of caffeine use after chronic exposures leads to a withdrawal syndrome with headache as a dominant symptom. At dosages achieved by common dietary intake, caffeine acts as a potent antagonist of central and peripheral nervous system adenosine receptors. The complex effects of caffeine on headache disorders suggest important roles for adenosine in these disorders and in the induction of caffeine dependency.