The diverse selection of treatments for Rheumatoid Arthritis (RA) have had a complex evolution. Observational studies demonstrated the benefit of Non-Steroidal Anti Inflammatory agents and conventional synthetic disease modifying agents (DMARDs). Of the DMARDs, Gold and Sulfasalazine were employed in the assumption they were treating arthritis with an infectious aetiology. Glucocorticoids promised to be the cure they did not provide, initially side-lined due to their adverse effects. The conventional DMARD, Methotrexate remains the anchor drug to induce and maintain remission. The array of medications in use has widened with our deeper understanding of the complex pathogenic processes underlying RA. Treatments originally designed to treat sepsis resulted in the conception and use of targeted monoclonal antibodies (biologics). The demonstration of cytokine mediated autoimmunity present in RA has more recently led to the oral targeted synthetic alternatives, including the Janus Kinase(JAK) inhibitors. These medications do not come without a significant monetary and side effect cost. As we observe the mechanisms of drug development revolutionize, with safer mechanisms of drug delivery and the informative role of genomics, we can hope for less harmful and more efficacious targeted therapies for this chronic debilitating condition. Paying attention to the historical ways in which we have developed our drug formulary allows us to reflect upon and foster those techniques for the aim to reduce disease progression, strive for longer remission and possibly curative treatment.