Infection with non-1 genotype in Croatia is detected in 41.2% of patients with chronic hepatitis C. Since the last treatment guidelines for hepatitis C patients, little has been changed. With today's standard of care, sustained viral response can be achieved in 43% to 85% of non-1 CHC patients, which is not satisfactory at all. The lowest cure rate is usually found among patients with genotype 3 and 4 infection. The grouping of genotype 2 and genotype 3 patients to "easy to treat" genotypes was an unfortunate consequence of their underrepresentation in previous large registration clinical trials. Careful re-examination of the data obtained shows clearly enough that patients with genotype 3 infection respond less to treatment than genotype 2 patients. They sometimes behave more like patients with genotype 1 infection. Small progress is found in treatment approach and viral kinetics might be a useful tool for tailoring therapy to improve efficacy. Rapid virologic response is the best parameter to predict success of therapy. For patients who achieve a rapid viral response, consideration of shortened therapy (< 24 weeks) may be reasonable although sustained viral response is still slightly higher with 24 weeks of therapy. Nevertheless, the presence of poor prognostic factors (high viral load, advanced fibrosis, obesity, increased age, insulin resistance and liver non-viral steatosis) may discourage a shortened course of therapy. Extending therapy (> 24 weeks) in patients who do not achieve a rapid viral response would be beneficial, particularly in patients with genotype 3 infection and poor prognostic factors, but formal recommendation should be confirmed in prospective trails. New data suggest a prognostic role for IL28B polymorphisms mostly in genotype 3 patients not achieving a rapid viral response and these could also be considered for improved tailoring of therapy. In conclusion, new treatments are urgently needed for non-1 genotype chronic hepatitis C patients. So far, telaprevir and boceprevir have failed to show a satisfactory activity in these genotypes. Evaluation of many promising molecules such as second generation of protease inhibitors or NS5B nucleos(t)ide inhibitors, NS5A inhibitors, cyclophilin inhibitors or their combinations with or without pegylated interferon or ribavirin is still in progress.