To update the information on genetic markers influencing the outcome of hepatitis C virus (HCV) infection.Single-nucleotide polymorphisms (SNPs) in the region of the IL28B gene on chromosome 19, coding for the interferon (IFN)-λ3, are involved in HCV spontaneous and treatment-induced clearance, and may have an influence on liver fibrosis and inflammation in chronic carriers. The rs12979860 SNP has been recommended as single diagnostic genotype. IL28B variations are strongly associated with response to pegylated-IFN plus ribavirin (Peg-IFN/RBV) in patients with chronic infection by HCV genotype 1 or 4. Thus, the rs12979860 CC genotype is associated with a two-fold increase in the sustained virological response (SVR) rate in this setting. SVR is less influenced by IL28B variants in HCV genotype 2 or 3 carriers. The rs12979860 CC genotype frequencies vary among diverse genetic ancestor groups, explaining partly the differences in SVR among them. The underlying mechanisms are unclear, but it may involve the expression of IFN-stimulated genes in the liver. Inosine triphosphatase genotype is predictive of RBV-induced anemia, but its clinical usefulness is less straightforward than that of IL28B SNPs.IL28B genotyping can aid in Peg-IFN/RBV clinical decision-making, and it may be useful in the selection of candidates for triple therapy with Peg-IFN/RBV plus direct-acting antiviral drugs.