Increasingly, Veterans are prescribed potent opioid analgesics for the treatment of chronic pain despite limited evidence for efficacy and increasing evidence of serious harms including addiction and non-fatal and fatal overdose. While guidelines recommend consideration of dose increase for patients not benefitting from opioid therapy, the rates of major harms are directly related to dose. Higher doses may also be more likely to precipitate opioid-induced hyperalgesia, a paradoxical increased pain response, in susceptible individuals. In summary, opioid dose increase, a currently accepted clinical response to poorly controlled pain, may offer little benefit and certainly increases risk, especially in patients already on moderate-high doses (30-100 mg daily morphine equivalents). Alternative treatment strategies to opioid dose escalation that lessen risk and possibly increase benefit are much needed.