Situated between the circulation and the brain, the blood–brain barrier (BBB) protects the brain from circulating toxins while securing a specialized environment for neuro-glial signaling. BBB capillary endothelial cells exhibit low transcytotic activity and a tight, junctional network that, aided by the cytoskeleton, restricts paracellular permeability. The latter is subject of extensive research as it relates to neuropathology, edema and inflammation. A key determinant in regulating paracellular permeability is the endothelial cytoplasmic Ca²⁺ concentration ([Ca²⁺]_i) that affects junctional and cytoskeletal proteins. Ca²⁺ signals are not one-time events restricted to a single cell but often appear as oscillatory [Ca²⁺]_i changes that may propagate between cells as intercellular Ca²⁺ waves. The effect of Ca²⁺ oscillations/waves on BBB function is largely unknown and we here review current evidence on how [Ca²⁺]_i dynamics influence BBB permeability.