Breakthrough pain is a heterogeneous condition. Non-opioid analgesics are a diverse group of drugs. Non-opioid analgesics may have a role in the management of breakthrough pain. Data on the use of most non-opioid analgesics is limited. Paracetamol and non-steroidal anti-inflammatory drugs are generally used as around-the-clock medication, although they may also be used as rescue medication. Systematic reviews of oral NSAIDs have confirmed benefits in cancer pain. Midazolam has been used in the treatment of refractory incident pain secondary to bone metastases and there is the potential for its use in the management of breakthrough pain secondary to muscle spasm. Ketamine is employed in anaesthetic doses in the management of procedural pain and in the management of predominantly non-malignant breakthrough pain. There is conflicting evidence for the use of nitrous oxide in the management of breakthrough pain.