As novel therapies for liver fibrosis evolve, non-invasive measurement of liver fibrosis will be required to help manage patients with chronic liver disease. Although liver biopsy is the current and time-honored gold standard for measurement of liver fibrosis, it is poorly suited to frequent monitoring because of its expense and morbidity, and its accuracy suffers from sampling variation. At the current writing, serum markers and imaging methods are available and increasingly in use as alternatives to biopsy. However, many questions remain about their indications, accuracy, and cost-effectiveness, and more investigation is required before they are put into widespread use. The development of safe, inexpensive, and reliable noninvasive fibrosis measurement tools remains a research priority in clinical hepatology. (Hepatology 2006;43:S113–S120.)