Hepatitis Delta Virus (HDV) is associated with one of the most severe forms of viral hepatitis, with rapid progression to cirrhosis and hepatocellular carcinoma. While HDV was thought to be uncommon in the United States, recent data shows that its prevalence may be significantly higher than formerly acknowledged. Early identification of HDV is critical since approved therapeutic options are only available for compensated patients. All patients with a reactive hepatitis B virus surface antigen should undergo HDV screening, especially those with additional risk factors, including migration from an endemic area, immunosuppressed patients, hemodialysis patients, gay and bisexual men, persons who inject drugs, and persons employed in healthcare or public safety professions.