The fibrinolytic pathway is a highly orchestrated system and an important regulator of thrombosis and hemostasis. The intricate balance of the fibrinolytic system can be disturbed in non-physiological conditions like surgery and trauma. Antifibrinolytics agents have been used in different clinical settings to reduce or halt bleeding. Over the last three decades, accumulating evidence has confirmed their efficacy and safety in surgery-related bleeding, trauma, postpartum hemorrhage, and many other bleeding conditions. This review will focus on the common antifibrinolytic agents and evidence supporting their efficacy, indications, dosing, and adverse effects.