Liver biopsy is still the most reliable procedure for the diagnosis of chronic, diffuse liver disease, so it is performed routinely to elucidate chronic alterations of liver tests. However, expensive and invasive, it is not exempt from risk and has limitations due to sampling error and to the size and quality of the tissue obtained. Moreover, many patients who undergo liver biopsy get no further treatment or do not benefit from treatment when the biopsy results are known. In addition, new biochemical tests have been developed in recent years as noninvasive tools to diagnose liver diseases, particularly fibrosis and cirrhosis. Thus, the role of liver biopsy in the improvement of outcome and quality of life of patients with chronic, diffuse liver diseases should be reconsidered. Many liver biopsies might well be avoided with the rational use of these noninvasive methods without any deleterious effect on patient care. Current tests and future developments in this field should help us to select those patients who would best benefit from a liver biopsy.