An accompanying commentary suggests this association between tramadol use and hypoglycaemia is a causal one as many of the fundamental tests of causality are met. It notes other published and unpublished reports of tramadol use as a cause of hypoglycaemia, whilst animal studies provide evidence of a complex but incompletely characterised pathophysiologic mechanism. The authors wonder why hypoglycaemia is not seen in patients taking other μ agonists such as morphine, oxycodone and hydrocodone? They highlight that though there is a perception that tramadol is a safe analgesic not prone to abuse, its analgesic effects are at best moderate, its toxic effects are dangerous and merit respect, particularly when doses are escalated; and seizures, serotonin syndrome, drug interactions, and opioid-related adverse effects are now joined by the potential risk of hypoglycaemia. They advise clinicians to be vigilant for this potential complication of tramadol use, in patients taking the drug as directed, as well as those who abuse it. They add it is unclear whether tramadol should be particularly avoided in patients receiving hypoglycaemic drugs, but given the drug’s limited benefit and unpredictable pharmacological properties, it should be handled at least as carefully in these patients as in others.