IntroductionRheumatoid arthritis is a common debilitating autoimmune disease that affects men and women of different ages throughout the world. Methotrexate is a well-known initial treatment for rheumatoid arthritis, but is it enough? New studies are showing that a class of drugs known as TNF inhibitors decrease disease progression when used in addition to methotrexate in the early treatment of rheumatoid arthritis. Of the available TNF inhibitors, Enbrel and Humira are the most commonly used because they have the same mechanism of action and only require an injection once a week which allows for better compliance. Since they have the same mechanism of action, Enbrel and Humira can be used interchangeably and therefore will both be discussed in this review. One of the biggest challenges with the use of TNF inhibitors in the treatment of rheumatoid arthritis is knowing when to introduce them in addition to methotrexate. Should patients be given these TNF inhibitors early in the disease or when methotrexate monotherapy fails to reduce disease activity? This is a common question among patients and doctors. The goal of using these drugs together is to reduce disease activity to a low level with the possibility of inducing remission. The following paragraphs will review the most up-to-date studies and provide the information needed to understand how to best combine these drugs when treating patients with rheumatoid arthritis. Summary of Literature Review The studies for this review were found using the PubMed database through the Saint Louis University Medical School Library. The search criteria were limited to human studies conducted within the last 5 years in the English language with a focus on randomized control...... half of the article ...... e. This study was found to have many strengths and weaknesses. The main strength of the study was that it was double-blind, multicenter and placebo-controlled1. Other strengths included that the same doctor followed the same patients at each encounter to record the number of painful and swollen joints encountered; Patients were not permitted to use NSAIDs, and the analysis of results was purposive, so as long as patients received a Humira injection or placebo they were included in the results. Weaknesses included the fact that the study never mentioned how the two groups were randomized in the study; paracetamol could be taken freely by patients; the study authors were reimbursed; and triple therapy with sulfasalazine and hydroxychloroquine plus methotrexate was introduced in eighteen patients with Humira compared to twenty-seven patients with placebo1.