There is a need to rationalize the use of synthetic DMARDs to help improve RA treatment. One recommendation to assist the rationalization of this treatment is by the construction of suitable models of the disease process, thereby augmenting treatment options. Currently, the dosage and duration of this type of treatment is based on its overall effect and clinical outcome. Each DMARD will confer its effect on a specific component of the multilevel, multicellular, pathological process of RA. Furthermore, developing definitive biomarkers could help to better assess the disease at its various stages instead of using conventional RA measures for drug titration and to help in the rationalization of drug regimen. Integrating pharmacokinetic and pharmacodynamic properties into this model will also help in improving treatment outcomes.