Characterization of the chemistry, structure, formation, and metabolism of DNA adducts has been one of the most significant contributions to the field of chemical toxicology. This work provides the foundation to develop analytical methods to measure DNA adducts, define their relationship to disease, and establish clinical tests. Monitoring exposure to environmental and endogenous toxicants can predict, diagnose, and track disease as well as guide therapeutic treatment. DNA adducts are one of the most promising biomarkers of toxicant exposure owing to their stability, appearance in numerous biological matrices, and characteristic analytical properties. In addition, DNA adducts can induce mutations to drive disease onset and progression and can serve as surrogate markers of chemical exposure. In this perspective, we highlight significant advances made within the past decade regarding DNA adduct quantitation using mass spectrometry. We hope to expose a broader audience to this field and encourage analytical chemistry laboratories to explore how specific adducts may be related to various pathologies. One of the limiting factors in developing clinical tests to measure DNA adducts is cohort size; ideally, the cohort would allow for model development and then testing of the model to the remaining cohort. The goals of this perspective article are to (1) provide a summary of analyte levels measured using state-of-the-art analytical methods, (2) foster collaboration, and (3) highlight areas in need of further investigation.