Hepatitis C virus (HCV) remains a significant global health challenge, with approximately 50 million people living with chronic HCV as of 2024. Direct-acting antivirals (DAAs) have greatly improved treatment outcomes, achieving high cure rates, but challenges remain, including DAA access disparities, variable treatment responses, and resistance-associated substitutions (RASs). A comprehensive review of HCV is needed to address current challenges, including RASs and vaccine development. The review highlights progress in managing and preventing HCV, while emphasizing persistent barriers. The goal is to align with global health objectives to reduce the burden of chronic hepatitis and achieve its elimination by 2030. HCV was first identified in the 1980s and is a member of the Flaviviridae family, with seven major genotypes and numerous subtypes. Genetic diversity affects treatment responses and clinical outcomes. The HCV genome is a positive-sense RNA with a single open reading frame (ORF), encoding proteins essential for viral replication. HCV primarily infects the liver, with transmission mainly through percutaneous exposure to infected blood. Other transmission routes include mother-to-child and sexual contact. HCV infection can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Diagnosis involves serological tests and HCV RNA testing. Treatment has evolved from interferon-based therapies to DAAs, which are highly effective and well-tolerated. DAAs have revolutionized HCV treatment, with cure rates exceeding 95%. However, high costs limit access in low- and middle-income countries. Prevention strategies include universal HCV screening, harm reduction for injection drug users (IDUs), and treatment as prevention (TasP). Vaccines are still under development due to HCV's genetic variability and challenges in eliciting a protective immune response. The review underscores the need for ongoing research and updated guidelines to address HCV's global health impact.Hepatitis C virus (HCV) remains a significant global health challenge, with approximately 50 million people living with chronic HCV as of 2024. Direct-acting antivirals (DAAs) have greatly improved treatment outcomes, achieving high cure rates, but challenges remain, including DAA access disparities, variable treatment responses, and resistance-associated substitutions (RASs). A comprehensive review of HCV is needed to address current challenges, including RASs and vaccine development. The review highlights progress in managing and preventing HCV, while emphasizing persistent barriers. The goal is to align with global health objectives to reduce the burden of chronic hepatitis and achieve its elimination by 2030. HCV was first identified in the 1980s and is a member of the Flaviviridae family, with seven major genotypes and numerous subtypes. Genetic diversity affects treatment responses and clinical outcomes. The HCV genome is a positive-sense RNA with a single open reading frame (ORF), encoding proteins essential for viral replication. HCV primarily infects the liver, with transmission mainly through percutaneous exposure to infected blood. Other transmission routes include mother-to-child and sexual contact. HCV infection can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Diagnosis involves serological tests and HCV RNA testing. Treatment has evolved from interferon-based therapies to DAAs, which are highly effective and well-tolerated. DAAs have revolutionized HCV treatment, with cure rates exceeding 95%. However, high costs limit access in low- and middle-income countries. Prevention strategies include universal HCV screening, harm reduction for injection drug users (IDUs), and treatment as prevention (TasP). Vaccines are still under development due to HCV's genetic variability and challenges in eliciting a protective immune response. The review underscores the need for ongoing research and updated guidelines to address HCV's global health impact.