Hepatitis B is an important cause of morbidity and mortality around the world. One-third of the world's population has been estimated to be infected with hepatitis B virus (HBV). A significant amount of evidence suggests that both humoral and cellular immune responses are important to eliminate the virus and that, cellular immunity is involved in the pathogenesis of the disease. Vaccination with HBsAg is considered as the main strategy for effective control of the infection and viral transmission. However, approximately 5-10% of immunized individuals fail to elicit detectable specific antibodies and remain at risk for hepatitis B infection. In this work we have reviewed the current status in the pathogenesis of the disease and the mechanisms described to explain nonresponsiveness to the vaccine as well. Since nonresponders to the vaccine are at risk for the infection, a common mechanism to explain the absence or inappropriate immune response to virus components is proposed. Within the suggested model an impaired activation of T lymphocytes against viral antigens, both in nonresponders to vaccination and chronically infected patients, is described. These observations could be consistent with potential differences in the MHC/Ag presentation; therefore contributing to our understanding of the altered T helper response as an underlying mechanism for the lack of protective immunity against VHB.