Chronic hepatic disease damages the liver and the resulting wound-healing process might lead to liver fibrosis and subsequent cirrhosis development. Fibrosis is the excessive deposition of extracellular matrix (ECM) in the tissue as consequence of chronic liver damage. The fibrotic response triggers almost all of the complications of end-stage liver disease, including portal hypertension, ascites, encephalopathy, synthetic dysfunction and impaired metabolic capacity. Thus, efforts to understand and attenuate fibrosis have direct clinical implications. Reliable, accurate, disease-specific, noninvasive biomarkers of fibrosis and fibrogenesis in order to prevent or minimize the impact of the chronic liver disease progression are a critical need. This review aims to provide an overview of the possibilities that proteome technology can offer to the knowledge, diagnosis and prognosis of liver fibrosis.