Tau is a microtubule-stabilizing protein primarily localized in central nervous system neurons, but also expressed at low levels in astrocytes and oligodendrocytes. Tau consists of six isoforms in the human brain, with molecular weights of 48,000 to 67,000 daltons depending on isoform. Tau elevation is observed in the cerebrospinal fluid (CSF) of patients with neurodegenerative disease and head injuries, suggesting its extracellular release during neuronal damage and a role as a biomarker with specificity for brain injury. Potential movement of elevated CSF tau across the blood-brain barrier presents a possibility that measurements of tau in blood could provide a convenient peripheral window into brain/CSF status. Studies of tau in serum and plasma have been hampered by its low abundance (typically low pg/mL), and there are relatively few reports characterizing the appearance of tau in blood or evaluating the usefulness of this biomarker for brain injury assessment. Recent reports using digital immunoassay technology have shown elevation in peripheral tau associated with hypoxic brain injury, concussed hockey players, and repetitive minimal head injury in Olympic boxing. The Simoa™ Human Total Tau assay uses a combination of monoclonal antibodies that react with both normal and phosphorylated tau. With an epitope in the midregion of the molecule, the assay recognizes all tau isoforms.