More and more viral infections are treated with antiviral drugs, and resistance against these drugs is steadily increasing. Our aim is to give a general understanding of viral resistance and its clinical significance.This article is based on review of published literature on the subject, international recommendations and our own experience as a national reference laboratory for hepatitis viruses.Development of viral resistance is an increasing problem with long-term treatment of both latent and chronic viral infections and may be one of the reasons for clinical treatment failure. Susceptibility testing is therefore an important diagnostic tool in cases of suspected failure during antiviral treatment, and is also necessary for customising of treatment to each individual patient. In Norway, susceptibility testing is offered for HIV, HBV, CMV and influenza, whereas systematic surveillance for the time being is only performed on HIV and influenza resistance. Surveillance on viral resistance is necessary in order to choose the adequate empirical therapy and to monitor the spread of resistant virus in the population. Prevalence of resistance can be limited with infection control measures and appropriate antiviral treatment, especially used in combinations of effective drugs directed at different enzymes and proteins within the virus.