Pregnancy and puerperium are considered to be hypercoagulable states with increased incidence of thromboembolic events. During normal pregnancy, changes in the hemostatic mechanism involve increased stasis and increased coagulation factors and/or decreased levels of anticoagulant proteins such as protein C and protein S as well as enhanced thrombin generation and decreased fibrinolytic activity. The physiological or pathophysiological activation of hemostasis during pregnancy results in the generation of the so-called activation markers which increase, reflecting hypercoagulability and therefore representing an imbalance in the hemostatic system. The most interesting markers of hemostasis activation and, thus, of thrombin generation are: thrombin-antithrombin III complex (TAT), antithrombin III itself, prothrombin fragment 1+2 (F 1+2), fibrin monomer (soluble fibrin) and D-Dimer (which indicates also an increased fibrinolytic activity). Together with fibrinogen levels and platelet counts, the activation markers are useful tools in different pathological situations in pregnancy to predict and monitor the severity of the condition. Recently, a higher incidence of factor V Leiden mutation has been demonstrated in selected populations in whom thrombotic events developed during pregnancy and puerperium. Therefore, the combination of APC resistance/FV Leiden mutation and pregnancy may predict a high risk for thromboembolic phenomena. In newborns, the activation markers are elevated immediately after birth and decline to near adult levels during the first 24 h of life. During infections the activation markers are increased showing the same behavior as in the mature adult system. In neonates and children, the same etiologies can be responsible for acquired and inherited pathological hypercoagulable states as in the adult.