New models of hemostatic function emphasize the importance of clotting factor interactions with cells and highlight the central event of thrombin production. As the coagulation cascade has evolved into a scheme of overlapping phases of initiation, amplification and propagation, the relevance of plasma based coagulation assays are being brought into question. Since platelets are critical to both amplification and propagation of the thrombin signal, assays performed in the absence of platelets would appear to completely miss these events. The lack of sensitivity to platelet influences may explain the inability of the prothrombin time (PT) and the partial thromboplastin time (PTT) to detect/reflect the therapeutic and clinical effects of agents such as recombinant FVIIa. This article reviews several evolving technologies for measuring thrombin generation and hemostatic function in samples of plasma and whole blood. Such assays may better reflect global hemostasis and hold potential for detecting hypo- and hyper-hemostatic states as well as monitoring both hemostatic and anticoagulant agents.