The study of CNS pain-modulating pathways has led to important discoveries about the role of central nociceptive structures such as PAG and hypothalamus in the pathophysiology of episodic and chronic primary headaches. Functional neuroimaging studies have revealed that primary headaches are characterised by different patterns of activation of central pain modulatory structures. A future model of headache pathophysiology investigating the contribution of CNS pain-modulating pathways will probably increase our understanding of pain processing in primary headaches. Herein we review the neurophysiological approaches to assess central pain modulation in primary headaches with emphasis on the diffuse noxious inhibitory control, a form of endogenous pain inhibition. In addition, patients' data will be presented that highlights the utility of such methods for primary headache's pathophysiology and clinical monitoring.