The present manuscript represents an updated review on different aspects of immunology involved during hepatitis C virus infection in human beings. This includes a brief mention of HCV structure, presentation of viral components to host immune system, and ensuing immune response and immunopathogenesis occurring during HCV infection. The present article also highlights immunodiagnosis of HCV infection and the current status of immunotherapy available for HCV eradication. Its envelope protein, E2, is the primary mediator of virus attachment and cell entry. CD81 molecule on cell surface acts as a major receptor for viral entry into the host cells. Mature dendritic cells play an important role in presenting viral antigen, activate T-cells, and initiate anti-viral immune response. Relative T-cell populations and release of different cytokines from activated T-cells ultimately determine the clearance or persistence of HCV viremia through cellular and humoral immune responses. Natural killer (NK) cells constitute the first line of host defense against invading viruses by recruiting virus-specific T-cells and inducing antiviral immunity in liver. Diagnosis of acute or chronic hepatitis C virus (HCV) infection is established by serological assays for presence of antibodies against different sets of viral proteins during varied periods post infection. An effective immunotherapy and vaccine against HCV is still awaited.