The plasma membrane Ca2+ -ATPase (PMCA) is responsible for the fine, long-term regulation of the cytoplasmic calcium concentration by extrusion of this cation from the cell. Although the general kinetic mechanisms for the action of both, well coordinated hydrolytic activity and calcium transport are reasonably understood in the majority of cell types, due to the complex physiologic and biochemical characteristics shown by the hepatocyte, the study of this enzyme in this cell type has become a real challenge. Here, we review the various molecular aspects known to date to be associated with liver PMCA activity, and outline the strategies to follow for establishing the role of this enzyme in the overall physiology of the hepatocyte. In this way, we first concentrate on the basic biochemical aspects of liver cell PMCA, and place an important emphasis on expression of its molecular forms to finally focus on the critical hormonal regulation of the enzyme. Although these complex aspects have been studied mainly under normal conditions, the significance of PMCA in the calcium homeostasis of an abnormal liver cell is also reviewed.