Dynorphin (DYN) is a potent endogenous opioid peptide which binds with high affinity to the κ-opioid receptor and has lower affinity for other opioid and non-opioid [N-methyl-D-aspartate (NMDA)] receptors. This pharmacological profile may explain the conflicting results obtained with DYN in experimental pain models. Most recent literature suggests that DYN contributes to the spinal analgesic effects of cannabinoids. In neuropathic pain, DYN and its fragments seem to contribute to the allodynia via activation of spinal NMDAreceptors. Interestingly, DYN attenuates opioid withdrawal and tolerance. The present data do not clearly identify a role for DYN in clinical pain therapy; however, a preliminary report suggests that it provides effective pain relief in patients with chronic cancer pain.