After isolation of a hepatitis C virus genome in 1989, all donated blood samples have been analyzed by a sensitive screening system, which brought us 'safety transfusion' (free from HCV). However it is likely that about 170 million people around the world, more than 2 million people in Japan have already infected with HCV. Despite the numerous efforts, the lack of efficient cell culture system makes it difficult to develop HCV vaccine. Some novel strategies are engineered day by day that might be useful tools. Hereafter we must clarify the mechanisms of replication and infection in depth, to develop a vaccine that clear HCV from carrier.