Tapentadol shares with tramadol a mixed mechanism of action. It has no identified analgesically active metabolite and is not significantly metabolised by CYP450, thus overcoming some limitations of tramadol, including potential for pharmacokinetic drug-drug interactions and inter-individual variability due to genetic polymorphisms of CYP450. It is likely to expose less to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) and more to opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. As a conclusion, tapentadol represents an additional analgesic which some patients may benefit from after careful examination of their clinical situation, comorbidities and comedications.