The clinical presentation of pain in primary headache disorders, such as migraine and cervicogenic headache, shows that the trigeminal and cervical innervation territories frequently are not respected during an attack. Here we review evidence that trigeminal afferents innervating the meninges, and cervical afferents in the greater occipital nerve (GON), have synaptic convergent input onto the same second-order neurons in the trigeminocervical complex. Furthermore, dynamic changes of excitability in terms of a sensitization to noxious input may occur on the central neuron level. The possible role of segmental mechanisms in the spinal cord and of inhibitory projections from brainstem structures such as the periaqueductal gray (PAG) in pain processing is discussed in view of data using neurostimulation of peripheral nerves in pain modulation. Recent experimental animal and human studies have facilitated our understanding of the role of these basic mechanisms in the spread, referral, and maintenance of pain in headache.