Hepatitis delta virus is the causative agent of one of the most severe forms of human virus hepatitis. It is a small and simple pathogen whose genome consists of a single RNA molecule of 1.7 Kb that encodes for only one antigen. The virus almost completely relies on the host cell machinery for replication and propagation of infection. Despite its simplicity, several aspects of virus replication and pathogenesis still remain uncovered. An overview of virus structure and replication mechanisms as well as of its interaction with the hepatitis B virus is performed in this review.