Septo-optic dysplasia, a variable combination of absence of the septum pellucidum, optic nerve hypoplasia, and pituitary abnormalities, makes little embryologic sense: components arise from different tissues and processes at different times, it is seen often with porencephaly, which is asymmetric, and rarely with other midline findings, genetic causes are exceptional, and occasional absence of the pituitary stalk is developmentally anomalous. Vascular vulnerabilities of components, anatomical overlap with findings of hydranencephaly and porencephaly, and a decreased maternal age effect similar to that of other abnormalities with presumed vascular origins, suggest a vascular disruption sequence instead, possibly involving the proximal trunk of the anterior cerebral artery.