Purpose of Review: This review presents recent findings on the role of prostaglandins in migraine pathophysiology. Recent Findings: Experimental studies have shown that prostaglandins are distributed in the trigeminal-vascular system and its receptors are localized in the trigeminal ganglion and the trigeminal nucleus caudalis. Prostaglandins were found in smooth muscles of cranial arteries, and functional studies in vivo showed that prostaglandins induced dilatation of cranial vessels. Human studies showed that intravenous infusion of vasodilating prostaglandins such as prostaglandin E2 (PGE2), prostaglandin I2 (PGI2) and prostaglandin D2 (PGD2) induced headache and dilatation of intra-cranial and extra-cranial arteries in healthy volunteers. In contrast, infusion of non-dilating prostaglandin F2α (PGF2α) caused no headache or any vascular responses in cranial arteries. PGE2 and PGI2 triggered migraine-like attacks in migraine patients without aura, accompanied by dilatation of the intra-cerebral and extra-cerebral arteries. A novel EP4 receptor antagonist could not prevent PGE2-induced headache in healthy volunteers. Summary: Recent in-vitro/in-vivo data demonstrated presence and action of prostaglandins within the trigeminal pain pathways. Migraine induction after intravenous administration of PGE2 and PGI2 suggests a specific blockade of their receptors, EP and IP respectively, as a new potential drug target for the acute treatment of migraine.