Dr. Seeff and colleagues present an update of a previously reported cohort of transfusion hepatitis patients now observed for approximately 25 yr. All-cause mortality was 67% among 222 hepatitis C cases and 65% among 377 controls. However, liver-related mortality increased further from previous reports to 4.1% versus 1.3% for controls. The etiology for transfusion hepatitis included 70% hepatitis C virus (HCV) and 30% non-A-G. Interestingly, 23% originally infected with HCV had spontaneously lost HCV RNA. The difficulty of studying the natural history of viral hepatitis cannot be understated. Dr. Seeff and colleagues have largely reported these important but difficult studies by analysis of stored serum and diligent follow-up. Detailed analysis of the HCV patients noted that 77% remained viremic, 49% had abnormal liver tests, and 35% of the positive HCV RNA patients with histological evidence of chronic active hepatitis progressed to cirrhosis. The next pivotal step shifts to identify risk factors that will predict progression of disease. This study further illustrates that a diagnosis of HCV or especially non-A-G hepatitis in the context of transfusions does not necessarily lead to a death sentence.