Hepatitis C virus (HCV) enters its target cells in a tightly regulated process that relies on several host factors. These host factors can be classified into three distinct categories depending on their role in the entry process, namely attachment factors, entry factors and facilitators. HCV entry is the target of host neutralizing anti-HCV antibody response. Furthermore, HCV entry is the first step of virus-host interaction and thus, in-part determines the hepato- and species tropism of the virus. Understanding HCV entry is, thus, not only crucial for development of novel entry-inhibitors and vaccine but also for developing new animal models to evaluate novel therapeutics and study disease pathogenesis. Research in the last 25 years has given unprecedented insights into the molecular aspects of HCV entry and its intricate association with the host. This review summarizes our current knowledge of the host factors involved in HCV entry and the molecular mechanisms determining the entry process.