Ligand-PET studies are attracting increasing interest in experimental and clinical research. As the most elaborated of PET techniques, ligand-PET allows the demonstration of receptor distributions, and thus, the delineation of neurochemical pathologies in the disease state. Recent developments are promising that ligand-PET will even allow to characterize dynamic and short-term changes in neurotransmission and will tremendously add to the understanding of neurophysiology on the receptor level. In pain studies, mainly the mu-opioidergic agonist [(11)C]-carfentanil and the unspecific opioid receptor antagonist [(11)C]-diprenorphine are applied. Utilizing these ligands the thalamus, prefrontal and cingulate cortex, basal ganglia and midbrain structures have been shown to possess high amounts of opioidergic receptors in vivo and it is well accepted, that the receptor density is higher in projections of the medial than those of the lateral pain system. Changes in receptor availability were observed in patients suffering from chronic pain. Rheumatoid arthritis, trigeminal neuralgia and central poststroke pain (CPSP) all lead to decreased ligand binding in pain processing regions during the painful period in comparison to pain free intervals or healthy subjects. These decreases may either be the consequence of increased endogenous release or indicate receptor internalization/down-regulation or loss of neurons carrying these receptors. Recent studies also evidenced [(11)C]-carfentanil binding changes due to acute experimental pain. One possible interpretation of these changes is that the PET-ligand might be displaced by endogenous opioidergic ligands. One major region, where this "ligand displacement" was observed, was the thalamus. These findings highlight the importance of the opioidergic system in pain processing and the power of ligand-PET to advance the understanding of pain.