This episode explores the Hepatitis B virus (HBV), covering its virology, the diseases it causes, its transmission, global prevalence, immunology, and treatment strategies. Against the backdrop of a high global burden of chronic HBV infection, the discussion delves into the complexities of acute versus chronic HBV, highlighting the significant challenges in diagnosis and treatment, particularly in resource-limited settings. More significantly, the panelists discuss the virus's unique replication cycle, its non-cytopathic nature, and the role of immune responses in disease progression and oncogenesis. For instance, the impact of viral integration into the host genome and the role of immune dysfunction in chronic infection are analyzed. The conversation then pivots to current and emerging therapies, including nucleoside analogs, capsid assembly modifiers, and immune-based approaches, along with the concept of a functional cure. Finally, the episode underscores the importance of preventative vaccines and the ongoing research into therapeutic vaccines to combat this globally significant virus, emphasizing the need for improved diagnosis, treatment, and public health initiatives.