The standard treatment of HCV infection with pegylated interferon-alpha2a or -alpha2b and ribavirin is effective in <50% of HCV genotype-1-infected patients. To improve this figure, it might be desirable to obtain optimal plasma concentrations of the drug by increasing the dose. Unfortunately, there is great interpatient variability in ribavirin pharmacokinetics. In the present review, we describe the mechanism of ribavirin-induced anaemia in detail, evaluate host predictive factors for this harmful side effect and assess the literature data on attempts to improve the sustained virological response rate by increasing the dose of ribavirin. We suggest an optimal steady-state concentration range for ribavirin in monoinfected and coinfected patients. Lastly, we propose that it would be of particular value to monitor ribavirin concentrations in HCV genotype-1-infected patients and (regardless of the genotype) coinfected patients, haemodialyzed patients and obese patients.