It is estimated that 71 million people are infected with hepatitis C virus (HCV), and they have an increased risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). Despite the high efficacy of direct acting antivirals (DAAs) not all patients successfully clear HCV infection, around 1-3% of treated patients fail to achieve sustained virological response 12 weeks off therapy (SVR12). DAA failures are characterized by advanced liver disease, specific genotypes/subtypes and resistance associated substitutions (RAS) to the DAA class. The Taiwan HCV Registry (TACR) programme recently reported that the factors associated with DAA failure was DAA adherence < 60%, GT3/GT2 infection active HCC, the use of sofosbuvir/ribavirin and daclatasvir/asunaprevir, decompensated liver cirrhosis and high baseline HCV viral loads. There are no clear guidelines on how to re-treat patients who fail DAA therapy, especially in Asia. Recent re-treatment guidelines suggest that >90% of patients with prior DAA failures can be successfully re-treated with sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir if genotype, fibrosis, treatment history and RAS are taken into consideration.