Immigration is fuelling a new reservoir of hepatitis D virus (HDV) in Europe, and hepatitis D still represents an important medical problem in the USA. The disease continues to be a major medical scourge in the developing world, in particular in countries such as Pakistan, Mongolia and Mauritania. New therapeutic strategies are being developed to disrupt interactions between HDV and its viral partner HBV, or with the host. Blocking or modifying the hepatitis B surface antigen (HBsAg) might interfere with the uptake or release of the hepatitis D virion; interference with host-mediated post-translational changes of proteins that are crucial to the HDV life cycle, such as prenylation, is another potential therapeutic option. At present, however, the only realistic option is to optimize IFN-α therapy. As eradication of HBsAg is the ultimate end point of therapy, long-term interferon administration might be required, raising an issue of tolerance in patients. Treatment with IFN-λ is a potential alternative approach to IFN-α; treatment of hepatitis C with this cytokine seems to cause fewer adverse effects than IFN-α and, therefore, might be more suitable for long-term treatment of HDV.