The cardinal symptom of migraine is headache pain. In this paper we review the neurobiology of this pain as it is currently understood. In recent years, we discovered that the network of neurons that sense pain signals from the dura changes rapidly during the course of a single migraine attack and that the treatment of an attack is a moving target. We found that if the pain is not stopped within 10-20 minutes after it starts, the first set of neurons in the network, those located in the trigeminal ganglion, undergo molecular changes that make them hypersensitive to the changing pressure inside the head, which explains why migraine headache throbs and is worsened by bending over and sneezing. We found that if the pain is not stopped within 60-120 minutes, the second group of neurons in the network, those located in the spinal trigeminal nucleus, undergoes molecular changes that convert them from being dependent on sensory signals they receive from the dura by the first set of neurons, into an independent state in which they themselves become the pain generator of the headache. When this happens, patients notice that brushing their hair, taking a shower, touching their periorbital skin, shaving, wearing earrings, etc become painful, a condition called cutaneous allodynia. Based on this scenario, we showed recently that the success rate of rendering migraine patients pain-free increased dramatically if medication was given before the establishment of cutaneous allodynia and central sensitization. The molecular shift from activity-dependent to activity-independent central sensitization together with our recent conclusion that triptans have the ability to disrupt communications between peripheral and central trigeminovascular neurons (rather than inhibiting directly peripheral or central neurons) explain their clinical effects. Both our clinical and pre-clinical findings of the last five years point to possible short- and long-term advantages in using an early-treatment approach in the treatment of acute migraine attacks.