For the clinical management of acute and chronic pain, a possible therapeutic approach is the association between two or more drugs, which produce their biological effects on two or more different sites of action, in order to modulate directly or indirectly profile analgesic and adverse effects. Given the advantages of polypharmacology, in the drug discovery process has been established the strategy "one-molecule multiple targets". Considering that the various mediators involved in the circuit of pain represent potential targets for different pharmacological interventions, opioid-opioid or non-opioid-opioid multitarget ligands are potential drug candidates for the management of pain conditions. Multitarget ligands, able to act simultaneously on multiple opioid receptors subtypes, showed low propensity to induce side effects. Three chapters constitute this contribution; the first is focused on pain mechanisms and mediators and examine the main drugs clinically used. The second chapter list known multitarget opioid ligands. Finally, the third chapter deal with the LP1 pharmacological fingerprint, a suitable drug candidate for acute and chronic pain management.