The use of tumor necrosis factor-α (TNF-α) inhibitors has been increasing especially in patients with rheumatoid arthritis (RA). As TNF-α inhibitors are strongly immunosuppressive, the occurrence of hepatitis B virus (HBV) reactivation has recently been observed. Reports suggest a higher risk of complicating HBV reactivation in carriers who are treated with TNF-α inhibitors. Therefore, HBV carriers are recommended to undergo prophylactic administration of nucleos(t)ide analogs (NAs). Our literary analysis uncovered several characteristics of de novo hepatitis B due to TNF-α inhibitors. First, the time between the start of TNF-α inhibitors and the occurrence of de novo hepatitis was longer than one year. Second, patients were usually treated with additional non-biologic agents, which also had immunosuppressive effects. Third, the disease could be fatal. Fourth, several types of TNF-α inhibitors exhibited a risk of developing de novo hepatitis. Although the incidence of de novo hepatitis B varied among reports (0-5%/year), it is suggested that patients with prior HBV infection are at risk of developing de novo hepatitis due to TNF-α inhibitors. Many reports maintain that regular measurement of HBV DNA is effective in preventing de novo hepatitis. Prophylactic administration of NAs is also considered useful to avoid de novo hepatitis, although the issue of cost-effectiveness needs to be addressed. Lastly, whereas maintenance of circulating anti-HBs titer using HB vaccines may be effective in responders to prevent de novo hepatitis, further studies are required to clarify the utility of HB vaccination.