<p>Gelation of blood plasma is key to normal hemostasis. The regulation of coagulation in blood flow has been studied for several decades, but the key problems in the field remain unresolved. Understanding the major mechanisms governing coagulation under flow conditions is important for the development of new diagnostic tools, therapeutic agents, and novel strategies addressing pathological states associated with both hypo- and hypercoagulation. In this review, we highlight the general features of plasma coagulation under flow conditions, including its spatiotemporal dynamics and threshold dependence on the key parameters. A short overview of in vitro and in silico models and important breakthroughs that became possible with their combination is followed by a brief introduction into the analysis of the balance between convection, diffusion, and reactions using Peclet and Damköhler numbers. We highlight the major unresolved challenges in the field and share an overall perspective of the future directions that might help to clarify the important questions that emerged during the last decade of intensive research.</p>