There are four basic approaches to cancer pain control: modify the source of pain, alter central perception of pain, modulate transmission of pain to the central nervous system, and block transmission of pain to the central nervous system. Systemic pharmacologic management aimed at the first three of these approaches is the cornerstone of the treatment of most cancer patients with moderate to severe pain. Optimal pharmacologic management of cancer pain requires selection of the appropriate analgesic drug; prescription of the appropriate dose; administration of the analgesic by the appropriate route; scheduling of the appropriate dosing interval; prevention of persistent pain and relief of breakthrough pain; aggressive titration of the dose of the analgesic; prevention, anticipation, and management of analgesic side effects; consideration of sequential trials of opioid analgesics; and use of appropriate co-analgesic drugs for specific pain syndromes. Most clinicians should be able to control most of the pain in most of their cancer patients. Collaboration with pain and hospice/palliative care experts should help the rest. No cancer patient should live or die with unrelieved pain.