Background: Hepatitis B virus (HBV) continues to be a significant global health issue, impacting millions of people around the globe. Although antiviral medications have greatly enhanced the treatment of chronic HBV infection, the development of antiviral resistance presents a difficult obstacle to current therapeutic approaches. This review analyses the progression of antiviral resistance in HBV, providing insight into the underlying mechanisms and consequences for clinical treatment. The use of nucleos(t)ide analogues (NAs) and interferon-based therapy represented important achievements in the management of chronic HBV infection. Nevertheless, the extended utilization of nucleoside analogues (NAs), such as lamivudine, entecavir, and tenofovir, has been linked to the emergence of resistance mutations in the gene responsible for viral polymerase. These modifications provide the virus with a specific benefit, which reduces the effectiveness of antiviral drugs and requires changes in treatment. Moreover, the presence of both wild-type and drug-resistant strains inside the same patient exacerbates the complexity of treatment outcomes. The emergence of HBV antiviral resistance highlights the significance of diligent surveillance and prompt intervention to enhance treatment results and presents a substantial risk to current therapeutic approaches. Continued research endeavours to comprehend the genetic and molecular foundation of resistance, together with the creation of innovative antiviral substances, are crucial to tackle this problem and improve the long-term control of chronic HBV infection.