Recent technological advancements have improved the sensitivity and specificity of blood-based biomarkers for Alzheimer's disease (AD) and related dementias. These biomarkers, including amyloid-β (Aβ) peptides, phosphorylated tau (pTau) isoforms, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), allow for the characterization of neurobiological processes in a cost-effective and minimally invasive manner. While primarily used for research, these biomarkers have the potential to significantly impact clinical settings by aiding in diagnosis, predicting disease risk, and monitoring disease progression. Plasma NfL has shown promise as a non-specific marker of neuronal injury, while plasma pTau181, pTau217, pTau231, and GFAP have demonstrated high sensitivity and specificity for identifying AD pathology and dementia. This review provides an overview of commonly used blood-based biomarkers, discusses how comorbid medical conditions, demographic, and genetic factors influence their interpretation, describes ongoing efforts to move these biomarkers into clinical practice, and highlights the role of clinical neuropsychologists in contextualizing and communicating biomarker results to patients. The authors anticipate that blood-based biomarkers will be widely used in clinical settings for etiological diagnosis, quantifying disease risk, prognostication, monitoring disease status, and predicting treatment responsiveness. However, establishing clinically relevant biomarker cut-points and addressing the impact of comorbidities and genetic factors are crucial challenges.Recent technological advancements have improved the sensitivity and specificity of blood-based biomarkers for Alzheimer's disease (AD) and related dementias. These biomarkers, including amyloid-β (Aβ) peptides, phosphorylated tau (pTau) isoforms, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), allow for the characterization of neurobiological processes in a cost-effective and minimally invasive manner. While primarily used for research, these biomarkers have the potential to significantly impact clinical settings by aiding in diagnosis, predicting disease risk, and monitoring disease progression. Plasma NfL has shown promise as a non-specific marker of neuronal injury, while plasma pTau181, pTau217, pTau231, and GFAP have demonstrated high sensitivity and specificity for identifying AD pathology and dementia. This review provides an overview of commonly used blood-based biomarkers, discusses how comorbid medical conditions, demographic, and genetic factors influence their interpretation, describes ongoing efforts to move these biomarkers into clinical practice, and highlights the role of clinical neuropsychologists in contextualizing and communicating biomarker results to patients. The authors anticipate that blood-based biomarkers will be widely used in clinical settings for etiological diagnosis, quantifying disease risk, prognostication, monitoring disease status, and predicting treatment responsiveness. However, establishing clinically relevant biomarker cut-points and addressing the impact of comorbidities and genetic factors are crucial challenges.