Friedrichsdorf SJ - Commonly used opioids in Pediatric Palliative Care were reviewed with a special emphasis on tramadol and methadone, the 2 potentially particularly effective multimechanistic opioids. Due to its multimechanistic action profile, methadone seems to be one of the most effective and most underutilized opioid analgesics in children with severe unrelieved pain at end of life. Close monitoring of its effects for several days is emphasized, particularly when it is first started and after any dose changes. In children with progressive neurologic, metabolic, or chromosomally based condition with impairment of the central nervous system, tramadol seems to play a key role in treating episodes of inconsolability. However, as per recent 2017 United States Food and Drug Administration warning, pediatric use of tramadol should be restricted. This seems not to be based on clinical evidence, and therefore puts children at risk for unrelieved pain or increased respiratory depression.