The use of neurolytic blockade is a staple in the management of cancer pain. However, the data on neurolysis for chronic pain are plagued by inconsistencies in patient selection, diagnostic criteria, technical standards, and outcome measures. No one neurolytic agent or technique has been proven superior to another. Current evidence suggests that patients with pain of malignant origin may benefit from a variety of neurolytic techniques, as the benefit of documented short-term pain relief may outweigh risk at the end of life. In the absence of compelling data suggesting low-risk long-term efficacy, neurolysis for chronic benign pain should be cautiously considered, in most cases, only after failure of aggressive multidisciplinary management.