Morphogenesis of the blood-brain barrier (BBB) is a complex process linked to neovascularization of the embryonic neural tube. This selective transport interface forms between vascular-neural compartments during organogenesis and dysregulation has been linked to neuroinflammation and neurodevelopmental defects. One emerging concept is that microglial cells play a central role in this neurovascular patterning, yet despite an extensive literature base, many gaps still exist in understanding how this resident immunological sentinel cell type interacts with chemical exposure at critical stages of neurodevelopment. The goals of this short review were to: (i) synopsize current understanding of microglial function during BBB morphogenesis; (ii) review potential disruption of microglial function linked to drug/chemical exposure during pregnancy; and (iii) present a working computational model for predictive toxicology of BBB dysmorphogenesis.