Disregarding pain resulting from vitamin deficiency, an analgesic effect seems to be exerted only by vitamin B1 (thiamine), vitamin B6 (pyridoxines), and vitamin B12 (cobalamine), particularly when the three are given in combination. The analgesic effect is attributed to an increased availability and/or effectiveness of noradrenaline and 5-hydroxytryptamine acting as inhibitory transmitters in the nociceptive system. In animal experiments, high doses of these vitamins administered alone or in combination inhibited nociceptive behavior and depressed the nociceptive activity evoked in single neurons of the dorsal horn of the spinal cord and in the thalamus. Moreover, they were found to enhance the antinociceptive effect of non-opioid analgesic agents on withdrawal reflexes. Clinical data fail in most cases to meet current standards of evaluation (randomization, double-blindness). Still, it appears that high doses of the vitamins B1, B6, and B12 administered separately or in combination can alleviate acute pain and potentiate the analgesia caused by non-opioid analgesics such as the NSAIDs and metamizol (dipyrone). Therapeutic effects are observed in neuropathic pain and pain of musculoskeletal origin. Vitamin B6 is effective in the carpal tunnel syndrome which, however, is attributed at least in some cases to vitamin B6 deficiency. It is also worth noting that the B vitamins are shown to enhance the beneficial effect of diclofenac in acute low-back pain so that either the duration of treatment or the daily dose of diclofenac may be reduced. The use of high doses of vitamin B6 may be limited by a neurotoxic effect. The effectiveness of B vitamins in depressing chronic pain has not been established. It would be interesting to know if the B vitamins are of use as adjuvants in the treatment of tumor pain.