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Purpose of Review: The aim of this study is to highlight the recent findings on the use of methotrexate and/or TNFalpha-blockers in adult patients with rheumatoid arthritis and their effects on the immune response to various vaccines., Recent Findings: Regarding influenza vaccination, methotrexate monotherapy is not associated with a decreased response, whereas the use of etanercept and infliximab in combination with methotrexate may cause lower titers and lower response rates. Concerning pneumococcal vaccination, methotrexate seems to impair responsiveness. The concomitant use of adalimumab and methotrexate is also associated with decreased response, whereas the concomitant use of etanercept or infliximab seems not to have an effect on response rates. As immunological pathways seem to play a major role, T-cell-dependent pneumococcal vaccines are designed to achieve higher response rates and protective titers., Summary: Patients with rheumatic disorders are more likely to develop preventable infectious diseases, which underlines the importance of adequate immunoprotective titers. Several studies have shown that the combination of methotrexate and certain TNFalpha-blockers are affecting the responsiveness to vaccines. Further findings indicate that the response also depends on what type of vaccine is used.