Oral tolerance is a method to alter the immune response towards orally administered antigens. The use of oral tolerance as a method of therapy for various immune mediated processes, including infectious, inflammatory and neoplastic entities, has been the subject of much research in recent years. The therapeutic potential of modifying the immune response by oral ingestion of diseaseassociated antigens is gaining recognition, and is being assessed in diverse settings. Studies have shown that anti-viral immunity can be modulated by oral feeding of viral proteins in animal models, and recent data suggest that this can also be achieved in humans. Oral administration of HBV-envelope proteins to patients with chronic HBV infection has been shown to be beneficial, not only for alleviation of immune-mediated liver injury but also for enhancement of effective anti-viral immunity. Several patents described the use of oral administration of viral particles as a mean of altering the anti viral immune response. Natural killer T (NKT) lymphocytes, a subset of regulatory T lymphocytes, can induce pro-inflammatory or anti-inflammatory immune responses. This subset of cells appears to be crucial for induction of tolerance by several interventions, including oral tolerance. This review summarizes the data on induction of tolerance towards viruses, and on the role of NKT regulatory cells in this setting. Several patents described the use of this method a treatment mode for viral infections and the use of NKT cells in this settings.