Studies conducted in recent years have helped define the role of antidepressant drugs in the management of cancer pain. The antinociceptive action of these agents seems to be independent of beneficial effect on depression or mood. Among antidepressant drugs, those of the tricyclic class are preferred when an analgesic effect is sought. Their primary application is for pain due to nerve injury, so-called "neuropathic pain". Although the co-administration of tricyclic antidepressants may increase plasma morphine concentrations, any potentiation of morphine analgesia is thought not to be due to an increased bioavailability of the opiate, but to an intrinsic analgesic effect of antidepressants. On this basis, the use of antidepressants in combination with opioids for the treatment of cancer pain is suitable when a component of deafferentation is present or when there is concomitant depressive illness.