Anna S. F. Lok reviews the current state of research on achieving a functional cure for chronic hepatitis B virus (HBV) infection. Current treatments, including pegylated interferon-α (pegIFN-α) and nucleos(t)ide analogues (NAs), can suppress HBV replication, reduce liver inflammation and fibrosis, and lower the risk of cirrhosis and hepatocellular carcinoma. However, HBsAg loss is rare, and a functional cure is defined as undetectable HBsAg and unquantifiable HBV DNA for at least 24 weeks after treatment. Achieving this requires suppressing HBV replication and restoring immune responses. Direct-acting antivirals targeting different stages of the HBV lifecycle and immune modulatory therapies are being tested in clinical trials. While individual therapies have not achieved HBV cure, combinations, particularly with pegIFN-α, have shown promise. However, larger studies with longer follow-up are needed to confirm these results. New therapies must provide incremental value compared to current NA therapy, which is long-term and has a good safety profile. Challenges include the persistence of covalently closed circular DNA (cccDNA) and integrated HBV DNA, which can continue to produce viral proteins. HBV cure also requires sustained suppression of these forms and restoration of immune responses. New therapies must be safe, effective, and simple to administer. Current trials show that combination therapies with direct-acting antivirals and immune modulators, especially those including pegIFN-α, may achieve HBsAg loss. However, long-term durability and the role of immune modulators remain uncertain. The definition of HBV cure includes sterilizing, functional, and partial cures. Functional cure is the goal, requiring sustained HBsAg loss and undetectable HBV DNA. Recent trials show that combination therapies can achieve this, but results need validation. New therapies must be tested for safety and efficacy, and their long-term impact on HBsAg loss must be determined. The development of simpler, more effective regimens remains a priority.Anna S. F. Lok reviews the current state of research on achieving a functional cure for chronic hepatitis B virus (HBV) infection. Current treatments, including pegylated interferon-α (pegIFN-α) and nucleos(t)ide analogues (NAs), can suppress HBV replication, reduce liver inflammation and fibrosis, and lower the risk of cirrhosis and hepatocellular carcinoma. However, HBsAg loss is rare, and a functional cure is defined as undetectable HBsAg and unquantifiable HBV DNA for at least 24 weeks after treatment. Achieving this requires suppressing HBV replication and restoring immune responses. Direct-acting antivirals targeting different stages of the HBV lifecycle and immune modulatory therapies are being tested in clinical trials. While individual therapies have not achieved HBV cure, combinations, particularly with pegIFN-α, have shown promise. However, larger studies with longer follow-up are needed to confirm these results. New therapies must provide incremental value compared to current NA therapy, which is long-term and has a good safety profile. Challenges include the persistence of covalently closed circular DNA (cccDNA) and integrated HBV DNA, which can continue to produce viral proteins. HBV cure also requires sustained suppression of these forms and restoration of immune responses. New therapies must be safe, effective, and simple to administer. Current trials show that combination therapies with direct-acting antivirals and immune modulators, especially those including pegIFN-α, may achieve HBsAg loss. However, long-term durability and the role of immune modulators remain uncertain. The definition of HBV cure includes sterilizing, functional, and partial cures. Functional cure is the goal, requiring sustained HBsAg loss and undetectable HBV DNA. Recent trials show that combination therapies can achieve this, but results need validation. New therapies must be tested for safety and efficacy, and their long-term impact on HBsAg loss must be determined. The development of simpler, more effective regimens remains a priority.