The on-treatment virological response to pegylated interferon plus ribavirin therapy is a useful tool in the management of patients with chronic hepatitis C. The time at which hepatitis C virus RNA becomes undetectable by a sensitive PCR assay has a huge impact on the probability of achieving a sustained virological response, particularly in genotype 1 patients, and may be useful in selecting patients for prolonged therapy. Indiscriminate extension of treatment in patients with hepatitis C virus genotype 1 is not beneficial. However, there is a subgroup of patients - the so-called 'slow responders' - who benefit from extending treatment from 48 to 72 weeks and can be readily identified after 4-12 weeks of combination therapy. Thus, it is important to distinguish slow responders from null responders. In the TeraVIC-4 study virological relapse rates were significantly lower, and sustained virological response rates were significantly higher, in those treated for 72 weeks with peginterferon alfa-2a (40 kDa) plus ribavirin (45% vs. 32% with 48 weeks, P=0.014). Patients are best served by quantitative determination of the hepatitis C virus RNA level at weeks 4, 12 and 24. The results of these determinations can then be used to tailor the length of therapy.