Protein Z is a vitamin K-dependent plasma protein described in its human form in 1984. The amino acid sequence of protein Z shows wide homology with many coagulation factors, such as VII, IX, X, and protein C. However, in contrast to other vitamin K-dependent coagulation factors, protein Z is not a serine protease because of the lack of the active centre in its amino acid sequence. The physiological function of protein Z has been uncertain for many years. In vitro and in vivo studies recently suggested that protein Z plays an important role in inhibiting coagulation, as it serves as cofactor for the inactivation of activated factor X by forming a complex with the plasma protein Z-dependent protease inhibitor. The role of alterations of the protein Z levels has been evaluated in different disease states, with conflicting findings. Most of these studies were performed on ischemic vascular diseases. Recently, the possible role of protein Z deficiency in the occurrence of cardiovascular diseases has been evaluated.