The need for a more precise test that replicates the in vivo hemostatic conditions is increasingly being recognized. Up to now, the thrombin generation assay (TGA) has become the most reliable approach to evaluate the status of coagulation activation. The clinical potential for the TGA is most promising in the prediction of venous thromboembolism recurrence. However, there is currently an urgent need for a standardized global test that can reliably detect, predict and monitor coagulation disorders in both clinical and experimental studies. We have recently modified the TGA to analyze not only tissue factor-driven coagulation, but the intrinsic coagulation pathway as well. In the present review, we discuss different TG tests, emphasizing the requirement for a better understanding of the evaluation of distinct coagulation pathways using this technique, as well as the standardization and clinical validation.