Procoagulant toxins are important hemotoxins that have been investigated both as laboratory reagents and potential therapeutic agents. In human envenomation by some elapid and many viperid snakes, these toxins result in venom-induced consumption coagulopathy. Overall, the coagulant activity of the various venoms is difficult to characterize, and many studies simply characterize toxin conversion of isolated substrates, such as the effect of a snake toxin on purified fibrinogen, or on multiple single substrates. As the full effects of toxins on the coagulation pathway are rarely examined, even in vitro, our understanding of the pathophysiology of envenoming is limited. Although prothrombin activators cause a single effect in vitro, there may be complete consumption of fibrinogen, factor V, and factor VIII in vivo due to the downstream effects of the thrombin that is formed. Laboratory diagnosis is a key part of the treatment of snakebite coagulopathy. Assessing which assays are the most informative in snake envenoming, based on the pathophysiology of snakebite coagulopathy, will optimize diagnosis and timing of appropriate coagulation tests. A better understanding of the coagulation effects arising from human envenoming will also improve treatment with antivenom and define the role of adjuvant therapies such as factor replacement.