Pain is a source of suffering in most advanced cancer patients, but many effective treatments exist. We updated previous systematic reviews on cancer pain treatment with targeted literature searches. Addressing pain involves comprehensive assessment, including other symptoms and sources of distress and barriers to pain management, and investigating potential etiologies and oncological emergencies when potential benefits exceed burdens. Initial treatment may involve acetaminophen or nonsteroidal anti-inflammatory agents, although opioids should be considered quickly if not effective or for severe pain. The initial approach also includes education and psychosocial interventions as appropriate. Neuropathic pain and bony pain may require specific interventions if initial treatment is not effective; the best evidence supports the use of gabapentin and single-fraction radiation, respectively. Potential spinal cord compression requires urgent evaluation and treatment. Most cancer pain can be effectively addressed with an evidence-based approach of medications, nonpharmacological approaches, and interventions when appropriate.