 Zika virus has recently been the center of a global pandemic. More devastating than the flu-like symptoms caused by infection are the fetal defects, such as microcephaly, that result in abortion, stillbirth, and death. Unfortunately, scientists have yet to grasp just how Zika reeks damage on the central nervous system. To that end, researchers from Brazil examined brain tissue from infants born with fatal microcephaly. Their findings offer useful clues to how Zika elicits immune responses that ultimately lead to neuronal cell death. The team compared tissue from 10 Zika-positive neonates with fatal microcephaly with tissue from five control neonates who died of causes other than Zika infection. They looked at three regions in particular, the meninges, the perivascular space, and the parenchyma. Their observations painted a circuitous pathway from the initial recognition of Zika by immune cells to two principal forms of nerve cell death, necrosis or premature cell death and apoptosis or programmed cell death. Upon recognizing Zika, dendritic cells may trigger neuroinflammation or signal a cavalry of white blood cells to release a series of proteins that modulate immune responses in different ways. These include pro-inflammatory proteins such as interleukin 9, 17, 22, and 23 that aggravate neuroinflammation and anti-inflammatory proteins such as interleukin 4, 10, 33, and 37 and transforming growth factor beta 1 that suppress immune responses, either directly or indirectly by signaling macrophages, astrocytes and neurons. These proteins contribute to necrosis or apoptosis. It's a rough picture of the incredibly complex interplay of triggered responses and action taken by Zika virus itself, but it could serve as a crucial roadmap for researchers and clinicians. The research team looks forward to further studies that could help clarify the full gamut of mechanisms and immune factors involved in the nervous system's response against Zika.