In the most recent years, therapy of chronic hepatitis has been improved. Nonresponder to an initial treatment is the predominant group of difficult-to-treat patients. Nonresponse may be due to host specific factors and/or virus specific properties. It is essential to reconsider the indication for treatment in respect to the presumed beneficial effect before initiating therapy or retreatment in these patients. Optimally, only those patients should be treated who are at significant risk for progression of liver disease.