There have been major advances recently in several areas of hepatitis C virus (HCV). The array of host receptors important for HCV entry now includes HSGP, LDLR, CD81, SRB1, CLDN1, occludin, and NPC1L1. The interaction of host and nonstructural viral proteins is essential for genome replication. Long-range interactions between cis-acting elements in the 5′ and 3′ UTRs and the NS5B coding region may control the switching between genome replication and genome packaging into virions, as well as modulate translation. Capsid assembly also involves NS5A, NS2, NS3/4A, and viral RNA as well as core protein. HCV assembly is intimately connected to host lipid metabolism and the synthesis of very-low-density lipoproteins (VLDLs) resulting in a lipoviroparticle. Core, NS5A, NS2, NS3, and NS4B can regulate host metabolic processes. HCV proteins have been shown to compromise host defenses at many levels, such as NS3 and NS5A inhibition of interferon alpha and NS5A and NS5B inhibition of apoptosis.