To evaluate the prevalence of past infection with hepatitis B virus (HBV) in patients with rheumatoid arthritis (RA) and the incidence of its reactivation under treatment with biological and/or nonbiological disease-modifying antirheumatic drugs (DMARDs), 239 patients receiving DMARD therapy were consecutively enrolled and tested for HBV-DNA, using a real-time polymerase chain reaction assay, HBV serology including hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc), and serum levels of aminotransferase. Data prior to DMARD therapy and during follow-up were examined by reviewing medical records. Two patients (0.8%) were positive for HBsAg at the start of therapy. Sixty patients (25.1%) showed HBsAg-negative and anti-HBc-positive serology indicative of past HBV infection. Among these 60 patients, 2 patients (3.3%) experienced reactivation of viral replication (<2.1 log copies/ml) during DMARD therapy. One had been receiving tacrolimus, prednisolone, and methotrexate (MTX); the other had been treated with adalimumab, prednisolone, and MTX. Their serum aminotransferase levels remained normal, and HBsAg was negative. Ten weeks after reactivation of viral replication had been noted, the HBV-DNA titer in the former patient had increased to 2.9 log copies/ml, and HBsAg and hepatitis B e antigen had become weakly positive. In contrast, the latter patient had become negative for viral DNA without any antiviral prophylaxis. In conclusion, the use of biological and nonbiological DMARDs is relatively safe in most RA patients with past HBV infection, even when no anti-HBV prophylaxis is administered. Considering the high prevalence of past infection in RA patients and the high cost of prophylaxis against HBV reactivation, universal prophylaxis is impractical. Regular monitoring of serum viral DNA seems to be the most rational approach to preventing the development of clinically apparent hepatitis.