Hepatitis B virus (HBV) infects over 300 million people globally and is a major cause of liver disease and liver cancer. It belongs to the Hepadnaviridae family, a small DNA virus with features similar to retroviruses. HBV replicates through an RNA intermediate and can integrate into the host genome, allowing persistent infection. Diagnosis and treatment of HBV-related diseases rely on virological and serological assays. HBV infection leads to a wide range of liver diseases, from acute hepatitis to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Acute HBV infection is often asymptomatic, but 5–10% of adults become chronically infected. Chronic HBV infection can progress to cirrhosis and HCC, requiring monitoring and treatment. Extrahepatic manifestations are rare but can be challenging to diagnose and manage. Challenges in HBV research include predicting disease progression and understanding the molecular, cellular, and genetic basis of HBV-related diseases. HBV has four overlapping open reading frames (S, C, P, X). The S ORF encodes surface envelope proteins, while the C ORF encodes core and polymerase proteins. The X ORF encodes HBxAg, which has multiple functions, including signal transduction and DNA repair. The HBV replication cycle involves viral entry, genome assembly, and replication. The viral genome is a partially double-stranded circular DNA of about 3.2 kb. HBV replication begins with encapsidation of the genome, followed by reverse transcription and synthesis of viral DNA. The cccDNA serves as a template for viral RNA transcription and is a key component of the replication cycle. Diagnosis of HBV infection involves serological markers such as HBsAg, HBeAg, and anti-HBc. HBV DNA testing is crucial for assessing viral replication and prognosis. Acute HBV infection typically presents with mild symptoms, while chronic HBV infection can lead to severe liver disease. Acute liver failure is rare but can occur in 1% of cases. Chronic HBV infection has a variable course, with some patients progressing to cirrhosis and HCC. Extrahepatic manifestations include conditions like serum-sickness-like syndrome, vasculitis, and nephropathy. Occult HBV infection, where patients are HBsAg-negative but have HBV DNA, is a significant concern due to potential transmission and persistent infection. Future research needs include understanding HBV's host interaction, the immunological basis of chronic infection, and the genetic factors influencing disease outcomes. These areas are critical for improving diagnosis, treatment, and prevention of HBV-related diseases.Hepatitis B virus (HBV) infects over 300 million people globally and is a major cause of liver disease and liver cancer. It belongs to the Hepadnaviridae family, a small DNA virus with features similar to retroviruses. HBV replicates through an RNA intermediate and can integrate into the host genome, allowing persistent infection. Diagnosis and treatment of HBV-related diseases rely on virological and serological assays. HBV infection leads to a wide range of liver diseases, from acute hepatitis to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Acute HBV infection is often asymptomatic, but 5–10% of adults become chronically infected. Chronic HBV infection can progress to cirrhosis and HCC, requiring monitoring and treatment. Extrahepatic manifestations are rare but can be challenging to diagnose and manage. Challenges in HBV research include predicting disease progression and understanding the molecular, cellular, and genetic basis of HBV-related diseases. HBV has four overlapping open reading frames (S, C, P, X). The S ORF encodes surface envelope proteins, while the C ORF encodes core and polymerase proteins. The X ORF encodes HBxAg, which has multiple functions, including signal transduction and DNA repair. The HBV replication cycle involves viral entry, genome assembly, and replication. The viral genome is a partially double-stranded circular DNA of about 3.2 kb. HBV replication begins with encapsidation of the genome, followed by reverse transcription and synthesis of viral DNA. The cccDNA serves as a template for viral RNA transcription and is a key component of the replication cycle. Diagnosis of HBV infection involves serological markers such as HBsAg, HBeAg, and anti-HBc. HBV DNA testing is crucial for assessing viral replication and prognosis. Acute HBV infection typically presents with mild symptoms, while chronic HBV infection can lead to severe liver disease. Acute liver failure is rare but can occur in 1% of cases. Chronic HBV infection has a variable course, with some patients progressing to cirrhosis and HCC. Extrahepatic manifestations include conditions like serum-sickness-like syndrome, vasculitis, and nephropathy. Occult HBV infection, where patients are HBsAg-negative but have HBV DNA, is a significant concern due to potential transmission and persistent infection. Future research needs include understanding HBV's host interaction, the immunological basis of chronic infection, and the genetic factors influencing disease outcomes. These areas are critical for improving diagnosis, treatment, and prevention of HBV-related diseases.