Methotrexate has become a standard therapy for the treatment of rheumatoid arthritis. This review summarizes the recent literature on low-dose methotrexate in the rheumatologic illnesses. The effect of methotrexate on in vivo rheumatoid factor production and suppression of ex vivo leukotriene B4 generation is reviewed. New information on drug interactions and pharmacokinetics is highlighted. The efficacy and toxicity of the drug in rheumatoid arthritis and other diseases are further defined. The effects of methotrexate on liver histology are also summarized.