Surveys indicate that clinicians are frequently ill equipped to treat cancer pain. Pain is often poorly assessed, and many caregivers lack sufficient knowledge to optimize treatment. Effective management requires an understanding of pain pathophysiology, the ability to identify and evaluate pain syndromes, and familiarity with proven therapeutic strategies. Opioid pharmacotherapy is the mainstay of treatment. Practical aspects of opioid therapy include selection of both drug and route, dose titration, and management of side effects. Specific strategies for the management of patients who are unable to attain an acceptable balance between pain relief and side effects include both noninvasive interventions (such as adjuvant analgesics, psychological therapies, and physiatric techniques) and invasive interventions (such as the use of intraspinal opioids, neural blockade, and neuroablative therapies). Sedation is an option at the end of life for the treatment of pain that is refractory to other interventions. These approaches can provide adequate relief to the vast majority of patients, most of whom will respond to systemic pharmacotherapy alone. Patients with refractory pain should have access to specialists in pain management or palliative medicine.