Psychomotor and cognitive dysfunction in cancer patients can be classified into two main categories according to etiology: disease-induced factors (metabolic disturbances, brain metastasis, pain, etc.) and treatment-related factors (drugs, antineoplastic therapy, etc.). In particular, the effects of chronic opioid administration in cancer patients have been subjected to investigations, and most studies have been engaged in assessment and treatment of the cerebral dysfunction. Early studies found that cancer patients in chronic oral opioid therapy had prolonged continuous reaction times, and that the opioids seemed to be mainly responsible for the prolongation. Significant dose escalations of opioids (> or = 30%) caused transiently impaired psychomotor and cognitive functions in cancer patients. Cancer patients in chronic oral opioid therapy did not achieve any advantages changing to epidural opioid therapy with regard to faster continuous reaction times and less pain. Large doses of opioids are often required to control severe pain in cancer patients. As increased sedation and impaired psychomotor and cognitive functions often occur, a number of studies have investigated the use of amphetamine derivatives to counteract the sedative side-effects of opioid. These drugs seem promising during high-dose opioid therapy and their use may be particularly rewarding in poor opioid-responsive pain conditions such as incident and neuropathic pain.