Summary: Tapentadol is a representative of a new class of centrally acting analgesics called MOR-NRI. It is a strong opioid with unique, dual mechanism of action: it is an agonist of the mu opioid receptor (MOR) and a noradrenaline reuptake inhibitor (NRI). Despite 50-fold lower affinity for the mu opioid receptor (MOR) compared to morphine, tapentadol has analgesic effects that is only 3-fold weaker than morphine. Such a strong analgesic effect of tapentadol is a result of the synergism of its two mechanisms of action. Each of these two mechanisms, as proven in experimental studies, plays a key role in different types of pain: the noradrenergic mechanism of action of tapentadol is largely responsible for its effectiveness in relieving various neuropathic pain syndromes, while its action on mu-opioid receptors (MOR) for analgesic effect of tapentadol in nociceptive pain. Many clinical studies confirmed good analgesic effect of tapentadol in treatment of acute postoperative pain and many chronic pain syndromes, including pain in the course of osteoarthritis, spinal pain syndrome (with or without a neuropathic component) or neuropathic pain. Available studies and everyday clinical practice also confirm the efficacy and safety of tapentadol in the treatment of severe pain in cancer patients. This article discusses the mechanisms of action, pharmacokinetics, potential adverse effects and drug interactions of tapentadol. It also presents a review of clinical studies assessing the efficacy and safety of tapentadol in the treatment of severe acute and chronic pain of non-malignant origin.