Derived from the same natural anticoagulant as warfarin (dicoumarol), long-acting anticoagulant rodenticides (LAARs) or superwarfarins have much longer half-lives in human blood than warfarin (weeks instead of hours) and are more potent inhibitors of the same enzyme, vitamin K epoxide reductase component 1. While used effectively worldwide as rodenticides, LAARs can elicit severe, protracted, life-threatening coagulopathy in humans at blood concentrations >10 ng/mL leading to numerous accidental and intentional poisonings annually. To facilitate timely identification and quantitative analysis of LAARs in patients presenting unexplained severe, protracted, life-threatening coagulopathy, several analytical methods have been developed, all of which are based on electrospray liquid chromatography-mass spectrometry (LC-MS). In this perspective, we evaluated and compared these LC-MS methods in terms of validation, simultaneous detection of multiple LAARs, measurement of individual stereoisomers, and clinical applications.