The publication of the Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage-2 (CRASH-2) study and its intense dissemination prompted a renaissance for the use of the antifibrinolytic agent tranexamic acid (TXA) in acute trauma hemorrhage. Subsequent studies led to its widespread use as a therapeutic as well as prophylactic agent across different clinical scenarios involving bleeding, such as trauma, postpartum, and orthopedic surgery. However, results from the existing studies are confounded by methodological and statistical ambiguities and are open to varied interpretations. Substantial knowledge gaps remain on dosing, pharmacokinetics, mechanism of action, and clinical applications for TXA. The risk for potential thromboembolic complications with the use of TXA must be balanced against its clinical benefits. The present article aims to provide a critical reappraisal of TXA use over the last decade and a “thought exercise” in the potential downsides of TXA. A more selective and individualized use of TXA, guided by extended and functional coagulation assays, is advocated in the context of the evolving concept of precision medicine.