The WHO analgesic ladder for the treatment of cancer pain provides a three-step sequential approach for analgesic administration based on pain severity that has global applicability. Nonopioids were recommended for mild pain, with the addition of mild opioids for moderate pain and strong opioids for severe pain. Here, we review the evidence for the use of nonopioid analgesic agents in patients with cancer and describe the mode of action of the main drug classes. Evidence supports the use of anti-inflammatory drugs such as acetaminophen/paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) for mild cancer pain. Adding an NSAID to an opioid for stronger cancer pain is efficacious, but the risk of long-term adverse effects has not been quantified. There is limited evidence to support using acetaminophen with stronger opioids. Corticosteroids have a specific role in spinal cord compression and brain metastases, where improved analgesia is a secondary benefit. There is limited evidence for adding corticosteroids to stronger opioids when pain control is the primary objective. Systematic reviews suggest a role for antidepressant and anticonvulsant medications for neuropathic pain, but there are methodologic issues with the available studies. Bisphosphonates improve pain in patients with bony metastases in some tumor types. Denosumab may delay worsening of pain compared with bisphosphonates. Larger studies of longer duration are required to address outstanding questions concerning the use of nonopioid analgesia for stronger cancer pain.