The liver function results from the interaction of anatomical, histological and biochemical aspects. Thus the concept of functioning liver mass must be related to the many biological aspects involved in the process under evaluation, and its measure can be viewed as a virtual parameter averaging the liver function. In the present review the functioning liver mass has been categorized with respect to the many aspects involved (biochemical transformations, membrane transports and passive intraluminal transports) and their interactions (intracellular, transcellular, transacinar and flow-dependent). Parameters reflecting the functioning liver mass (whether static or dynamic) have been considered with respect to the experimental conditions and characterized according to the type of estimate they provide (capacity or activity). Methods for evaluating the functioning liver mass have been presented and discussed, and a protocol has been proposed for clinical applications, based on the association of the galactose elimination capacity measuring the metabolic mass with the hepatic clearance of D-sorbitol evaluating the functional hepatic plasma flow.