The hepatitis B virus ( HBV) is a retroid virus that contains a small DNA genome with very limited coding capacity. Yet, HBV is extremely successful both atmultiplyingwithin individual host cells and at spreading across populations. In this review, wewill highlight some recent progress in understanding HBV-host cell interactions that are likely to contribute to the extraordinary ability of HBV to replicate and persist within the host cell, focusing primarily on studies carried out inmy own laboratory. The major HBV-cell interactions to be discussed include the role of cellular chaperones for the initiation of HBV reverse transcription and nucleocapsid assembly, host regulation of viral nucleocapsid maturation through the dynamic modulation of its state of phosphorylation, and the formation of the viral nuclear episomal DNA responsible for HBV persistence.