Hemostasis is maintained through interactions between whole-blood cellular components, the vascular endothelium, and pro- and anticoagulant plasma proteins such that net hemostasis is the result of the competing physiology of coagulation and fibrinolysis. Traditional hemostatic assessment involves plasma-based assays of coagulation proteins and evaluation of platelet number and function. This testing may not accurately reflect net hemostasis, as each test evaluates variables semi-independently and provides minimal/no information about fibrinolysis. Classic coagulation tests, including the prothrombin time (PT) and activated partial thromboplastin time (aPTT), were developed in the mid-twentieth century with little alteration other than automation since then. The PT measures the activity of the so-called extrinsic and common pathways of coagulation, while the aPTT measures the intrinsic and common pathways. Thrombin time (TT) measures the common pathway and reflects the conversion of fibrinogen to fibrin. The division of the clotting cascade into the intrinsic, extrinsic, and common pathways has little in vivo validity but has some conceptual utility in the interpretation of the results of laboratory investigation and for understanding laboratory testing. The fibrinolysis pathway contributes to maintenance of blood flow and hemostasis by prevention of unchecked coagulation and providing a mechanism for resorption of thrombosis but can result in abnormal bleeding in some clinical settings, such as when there is excessive activation in setting like trauma or post-partum hemorrhage.