The morbidity and mortality of chronic hepatitis C is related to progressive fibrosis and the development of cirrhosis. The development of fibrosis in patients with HCV is highly influenced by immune status, host response to the virus and associated factors, such as, age, sex, alcohol intake, diabetes, obesity and coinfection with other viruses. The rate of fibrosis progression differs depending on several factors, including the stage of fibrosis and the time since infection. Routine assessment of fibrosis through biopsy every 3-5 years has poor patient acceptance and reliability, and might result in missed opportunities to improve or modify treatment priorities. Enhanced understanding of the pathophysiology of liver fibrosis in HCV infection has led to the development of a number of non-invasive assessment modalities. The ideal test would discriminate fibrosis in the categories none/early (stages 0/1), intermediate (stage 2) and advanced fibrosis/cirrhosis (stages 3/4) and be readily available, inexpensive and accurate. Biomarker tests utilize individual or combined serum markers to determine the degree of fibrosis. Other strategies combine biomarkers with clinical variables, such as patient age or utilize liver imaging or functional assessments. Incorporation of appropriately validated non-invasive assessments of liver fibrosis will likely improve the clinical care of patients with HCV infection.