Hepatitis C virus (HCV) is the major causative agent of chronic non-A, non-B hepatitis. The life cycle of HCV is largely unknown because a reliable culture system has not yet been established. HCV presumably binds to specific receptor(s) and enters cells through endocytosis, as do other members of Flaviviridae. The viral genome is translated into a precursor polyprotein after uncoating, and viral RNA is synthesized by a virus-encoded polymerase complex. Progeny viral particles are released into the luminal side of the endoplasmic reticulum and secreted from the cell after passage through the Golgi apparatus. Understanding the mechanisms of HCV infection is essential to the development of effective new therapies for chronic HCV infection. Several host membrane proteins have been identified as receptor candidates for HCV. Recent advances using pseudotype virus systems have provided information surrounding the initial steps of HCV infection. An HCV RNA replicon system has been useful for elucidating the replication mechanism of HCV. In this review, we summarize our current understanding of the mechanisms of HCV infection and discuss potential antiviral strategies against HCV infection.