In clinical trials, neither control of HBV nor cure from chronic hepatitis B has been achieved using TLR agonists so far, indicating that the application of a TLR agonist may not result in induction of HBV-specific immunity, and triggering innate immunity and inflammation alone may not be sufficient to overcome immune tolerance and achieve control of chronic hepatitis B. However, alternative pattern-recognition receptor agonists triggering TLR8, Rig-I, or STING are currently evaluated in clinical trials; it will be interesting to see the outcome. The gene discussed is TLR8; the disease is chronic hepatitis B virus infection.