The blood-brain barrier (BBB) ensures brain function in vertebrates and insects by maintaining ionic integrity of the neuronal bathing fluid. Without this barrier, paralysis and death ensue. The structural analogs of the BBB are occlusive (pleated-sheet) septate and tight junctions between perineurial cells, glia and perineurial cells, and possibly between glia. Immature Diptera have such septate junctions (without tight junctions) while both junctional types are found in the imago. Genetic and molecular biology of these junctions are discussed, namely tight (occludin) and pleated-sheet septate (neurexin IV). A temporal succession of blood barriers form in immature Diptera. The first barrier forms in the peripheral nervous system where pleated-sheet septate junctions bond cells of the nascent (embryonic) chordotonal organs in early neurogenesis. At the end of embryonic life, the central nervous system is fully vested with a blood-brain barrier. A blood-eye barrier arises in early pupal life. Future prospects in blood-barrier research are discussed.