Vaccination is the main prophylactic measure to reduce the mortality caused by hepatitis B virus(HBV)infection in healthy subjects since the immune response to hepatitis B recombinant vaccination occurs in over 90%of general population.Individuals who develop an antiHBs titer less than 10 mIU/mL after primary vaccination cycle are defined“no responders”.Many factors could cause a non response to the HBV vaccination,such as administration of the vaccine in buttocks,impaired vaccine storage conditions,drug abuse,smoking,infections and obesity.Moreover there are some diseases,like chronic kidney disease,human immunodeficiency virus infection,chronic liver disease,celiac disease,thalassaemia,typeⅠdiabetes mellitus,down’s syndrome and other forms of mental retardation that are characterized by a poorer response to HBV vaccination than healthy subjects.To date it is still unclear how to treat this group of patients at high risk of hepatitis B infection.Recent studies seem to indicate that the administration of HBV recombinant vaccine by the intradermal route is very effective and could represent a more useful strategy than intramuscular route.This review focuses on the use of anti hepatitis B vaccine by intradermal route as alternative to conventional intramuscular vaccine in all non responder patients.A comprehensive review of the literature using PubMed database,with appropriate terms,was undertaken for articles in English published since 1983.The literature search was undertaken in September 2013. Vaccination is the main prophylactic measure to reduce the mortality caused by hepatitis B virus (HBV) infection in healthy subjects since the immune response to hepatitis B recombinant vaccination occurs in over 90% of general population. Individuals who develop an antiHBs titer less than 10 mIU / mL after primary vaccination cycle are defined “No responders ”. Many factors could cause a non response to the HBV vaccination, such as administration of the vaccine in buttocks, impaired vaccine storage conditions, drug abuse, smoking, infections and obesity. Recently there are some diseases, like chronic kidney disease, human immunodeficiency virus infection, chronic liver disease, celiac disease, thalassaemia, type Idiabetes mellitus, down’s syndrome and other forms of mental retardation that are characterized by a poorer response to HBV vaccination than healthy subjects. To date it is still unclear how to treat this group of patients at high risk of hepatitis B infection.Recent studies seem to indicate t hat the administration of HBV recombinant vaccine by the intradermal route is very effective and could represent a more useful strategy than intramuscular route. This review focuses on the use of anti hepatitis B vaccine by intradermal route as alternative to conventional intramuscular vaccine in all non responder patients .A comprehensive review of the literature using PubMed database, with appropriate terms, was undertaken for articles in English published since 1983. The literature search was undertaken in September 2013.