Viral infections, specifically chronic, markedly influence the host response to subsequent infections and vaccinations. Does this apply to chronic hepatitis C (CHC)? The review considers this question with implications for the immune status and functionality of the immune system of a chronically HCV-infected host. The data collected here indicate that CHC may increase the risk of viral superinfections and modify their course by immunocompromising the host. Patients with CHC do not lose the ‘memory’ of previous infections and vaccinations but, apparently, have problems with building such immunity anew, as illustrated by their impaired response to hepatitis A and B vaccinations. This underlines the necessity of extra protection of CHC patients against blood-borne diseases, hepatitis A, possibly also varicella, influenza, tetanus, and diphtheria – immunity to which, in the Western population, appears to falter. Such immune protection has to be adapted to selective impairments of immune response characteristic to CHC. Some approaches to this are reviewed here and more need to be elaborated. Special attention has to be given to CHC patients who do not respond to common vaccines; further studies in this field are of great interest.