Hepatitis B virus provides a model for studying the genetic variability and diversity of viruses. New molecular techniques such as the polymerase chain reaction and sequencing of amplified product enable the accurate pinpointing of genetic alteration. The immune response or lack of response to wild-type and mutant virus ultimately determines the extent of disease. Elimination of infection and disease may be achieved by natural, immunologic, and pharmacologic means, but definitive treatment may have to await the advent of gene therapy. Meanwhile, epidemiologic studies, vaccination programs, and cost-benefit analyses are important in the prevention and control of hepatitis B. Once the clinical and epidemiologic significance of mutant hepatitis B viruses is established, new strategies and vaccines will be required before elimination of the disease is achieved.