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The current review gives an overview about recent advances in neuroimaging studies with specific emphasis on pharmacological modulation of pain and headache. Further, we want to highlight how imaging methods have changed our understanding of chronic pain and discuss how pharmacological MRI could lead to new insights into underlying mechanisms of headache and pain.Several studies from different imaging laboratories have highlighted the outstanding role of imaging in getting a deeper insight regarding the central mechanisms of drugs. Neuroimaging techniques start to unravel how analgesic drugs, antidepressants or NSAIDs act on pain perception and in particular on central pain processes. Furthermore, the studies included in this review show how context dependent drugs act and how differently they reveal their action in the human brain.Imaging techniques give us the opportunity to gain a better understanding of drug processes in the central nervous system and help to understand where drugs reveal their therapeutic effect. While some substances work on the emotional-affective component of pain, others modulate sensory-discriminative pain pathways. Especially in the field of headache research, still a lot has to be done to understand how preventatives and acute medication modulate the human brain. Future studies should also replicate and extend recent findings.