Disease-modifying antirheumatic drugs (DMARDs) have largely contributed to recent paradigm shift of rheumatoid arthritis (RA) treatment strategy. DMARDs can be indicated for all RA patients and early use of DMARDs after diagnosis of RA is recommended. Individual DMARDs have common characteristics. Understanding these characteristics is very important in treating RA. As for safety, the pattern of adverse reactions (ADRs) associated with DMARDs has been generally understood. It is necessary to select DMARDs and follow up patients with recognition of the pattern of ADRs. Regular monitoring is also essential to ensure the safety of DMARDs. This chapter deals with some major DMARDs in Japan, including methotrexate, which is indispensable in current RA treatment; salazosulfapyridine and bucillamine; tacrolimus, which is recently increasing in use; and iguratimod, which became available in 2012.