Fluid biomarkers provide a quantifiable means to model and monitor disease progression in Alzheimer disease (AD). As usage of markers in the clinical realm expands, there is an increased need for novel, sensitive, and specific measures to accurately differentiate and distinguish stages of AD and other neurodegenerative diseases. Improvement in biomarker quality by selective assay platforms can allow for early detection or development of new markers, particularly when ultrasensitive or automated platforms are considered. Additionally, cerebrospinal fluid (CSF) biomarkers provide a backbone for the development and discovery of less invasive blood-based tests, while biomarker usage guidelines help bridge the gap between research and clinical usage. In order to produce robust biomarker data, it is important to consider and minimize the effects of pre-analytical factors (such as sample processing and handling) as well as analytical effects, including batch-to-batch variation within manufacturers, differences between assay platforms, and deviation from manufacturer protocols. Gold standard diagnostic assays, as defined by the US FDA, may also aid in clinical diagnosis. Biomarkers discussed in this chapter encompass traditional CSF markers of amyloid and tau pathology (Aβ40, Aβ42, total tau, and various species of hyperphosphorylated tau) as well as emerging CSF and blood-based markers of neurodegeneration (i.e., NfL, UCHL1, FABP and VILIP-1), neuroinflammation (i.e., GFAP and YKL-40), and synaptic integrity (i.e., Ng, SNAP-25 and synaptotagmin-1). Still, improvements in assay performance, standardization of sample handling and data analysis, and expanded biomarker assessments in diverse cohorts are necessary to advance our knowledge of fluid biomarkers in AD for broader applicability as the field moves forward.