Pain is difficult and sometimes frustrating to treat, even though new devices and new approaches have been developed in recent years. Pain varies tremendously from one patient to the next, and there are also some studies suggesting that the intensity of pain varies according to time of day. In animal experiments, a relationship between the reaction to pain and the rhythmicity of plasma endorphin concentrations was suggested because reactions to pain (such as jumping from a hot plate) were in phase with plasma endorphin levels, latencies were longest and plasma levels were highest during the resting period of rodents. In human studies, pain induced experimentally was reported to be maximal in the morning, or in the afternoon or at night. These divergent findings may be due to methodological differences, as pain was produced by different methods, many parameters were used to quantify pain intensity, and the psychological aspect of pain was rarely considered by authors. A circadian pattern of pain was found in patients suffering from pain produced by different diseases. For instance, highest toothache intensity occurred in the morning, while biliary colic, migraine, and intractable pain were highest at night. Patients with rheumatoid arthritis reported peak pain early in the morning, while those with osteoarthritis of the knee indicated that the maximal pain occurred at the end of the day. The effectiveness of opioids appears also to vary according to time of day, but large differences in the time of peak and low effects were found. Investigators found that peak pain intensity and narcotic demands occurred early in the morning, while others found maximal pain at the end of the day. Pain is a complex phenomenon and efforts should be made to standardize the methods used in studies and to describe accurately the diseases causing pain because the patterns of pain may be specific to each clinical situation. Further research should be aimed at characterizing the chronobiology of pain in different experimental and clinical situations and to determine when the analgesic drugs are producing maximal effectiveness. This information is needed before clinicians can be persuaded to use chronopharmacological data when they prescribe analgesic drugs to their patients.