Like all viruses, hepatitis B virus (HBV) replication and pathogenesis depends on the critical interplay between viral and host factors. In this review, we will focus on the recent progress in understanding the virus–host interactions at the level of the infected cell. These interactions include the requirement of cellular chaperones for the initiation of HBV reverse transcription, the role of the HBV X protein (HBx) in modifying viral and cellular transcription and signaling, the formation of the HBV episomal DNA and its epigenetic regulation in viral persistence, and the cellular factors involved in viral entry, nucleocapsid maturation, and virion secretion. J. Cell. Physiol. 216: 289–294, 2008. © 2008 Wiley-Liss, Inc.