Pain and other symptoms of advanced cancer are not treated effectively yet. This review of the literature discusses the needs and latest research findings about pain symptom assessment and management in palliative care. Pain assessment scores should not be followed blindly by a rigid therapeutic regimen. Instead, the health care provider should carefully consider the wide spectrum of possible underlying pain mechanisms. Unidimensional pain rating scales will not detect the impact of affective dimensions on pain expression as accurately as multidimensional rating scales that include various symptoms. Besides assessment tools like numeric rating scales or visual analogue scales, tools now frequently used in the daily clinical setting include the Edmonton Symptom Assessment System, the Mini Mental State Examination, and the CAGE questionnaire (Cutting down, Annoyance by criticism, Guilty feeling, and Eye-openers). Recent developments and findings in cancer pain management are illustrated by (1) the use of opioids like morphine, oxycodone, fentanyl, and especially methadone (which has been used increasingly as a secondline drug for opioid-resistant and neuropathic pain, and also for its low cost, long-acting nature, and low side-effect probability, especially in patients with renal failure resulting from the lack of active metabolites); (2) the use of adjuvant therapeutic agents like gabapentin, donepezil, dextromethorphan, and thalidomide; (3) the impact of the immune system on pain, with a concept of targeting immune cells that contain opioids to potentially enhance opioid production, the migration of these cells to tissue lesions, and the release of opioids at the peripheral site to achieve increased peripheral analgesia; and (4) approaches to pain imaging as well as the newly introduced interventions of vertebroplasty and kyphoplasty.