Chronic hepatitis C virus (HCV) infection is a major health problem worldwide. The natural history of HCV infection is not fully understood. For years, there has been an overestimation of the rate of chronicity in acute HCV. Similar high rates of progression to cirrhosis in chronic HCV were reported. The source of confusion stems from the fact that most acute HCV infections are asymptomatic and never come to medical attention. The consequence of this is that most early studies of natural history reflect the more severe end of the spectrum of the disease. Recent studies reported 43-45% rate of chronicity as opposed to the old rates of 77-85%. Also, the rate of progression to cirrhosis and hepatocellular carcinoma was found to be much lower than previously reported. Multiple factors contribute to the chronicity and progression to cirrhosis, the most important being male gender, age, alcohol intake, and the degree of liver fibrosis on initial biopsy. At least 38% of patients with HCV will manifest symptoms of at least one extrahepatic complication. The most important extrahepatic manifestation is mixed cryoglobulinemia. Other extrahepatic manifestations and their response to antiviral therapy are discussed.