HDV is a defective RNA pathogen requiring the simultaneous presence of HBV to complete its life cycle. Two major specific patterns of infection have been described: the coinfection with HDV and HBV of a susceptible, anti-HBs-negative individual, or the HDV superinfection of a chronic HBV carrier. Coinfection mostly leads to the eradication of both agents, whereas the majority of patients with HDV superinfection evolve to chronic HDV infection and hepatitis. Chronic HDV infection worsens the preexisting HBV-related liver damage. HDV-associated chronic liver disease (chronic hepatitis D) is characterized by necroinflammation and the relentless deposition of collagen culminating, within a few decades, into the development of cirrhosis and hepatocellular carcinoma.