Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive deterioration of cognitive functions, primarily memory, with evidence of the accumulation of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles (NFTs) in the brain. Related dementias include conditions such as Lewy body dementia (LBD), frontotemporal dementia (FTD), corticobasal syndrome (CBS), and vascular dementia, which exhibit similar cognitive impairments but are associated with different underlying pathologies at autopsy. The diagnosis of AD and related dementias (ADRD) involves comprehensive evaluations that include patient history, physical examination, neurological assessments, and cognitive testing. In recent years, commercial diagnostics using cerebrospinal fluid (CSF) and positron emission tomography (PET) scans have been increasingly used to detect the presence of Aβ plaques and tau proteins, providing a more accurate diagnosis. However, a definitive diagnosis is still largely dependent on clinical history followed by postmortem assessments. Research studies from the Dage lab at Eli Lilly were the first to demonstrate robust and reliable measurements, as well as clinical utility, of measuring phosphorylated tau (P-tau) forms in plasma. Now, several P-tau immunoassay tests are rapidly advancing into clinical trials and practice. Biomarkers of tau pathology accessible in living subjects are of great importance to understand the development and role of tau pathology in the onset and progression of neurodegenerative diseases. In addition, ongoing treatment trials targeting tau pathology now call for reliable and quantifiable tau biomarkers for the early identification of eligible study participants and the in vivo quantification of potential treatment effects. In this chapter, we summarize the current state of biofluid biomarkers of tau pathology and explain the association of plasma P-tau217 levels with Alzheimer’s disease neuropathologic change (ADNC).