Evidence from randomized controlled trials with newly approved DMARD therapies have proven efficacy by American College of Rheumatology [ACR] response criteria, Disease Activity Scores [DAS] and radiographic measures of disease progression. Treatment over 2 years duration results in clinically meaningful improvements in physical function, by the Health Assessment Questionnaire [HAQ] and health related quality of life [HRQOL], using the medical outcomes short form 36 [SF-36]. Changes in HAQ are evident within one month, maximal at 3-6 months, and sustained over 24 months, reflected by improvements in social functioning, role emotional and the general health profile as well as physical domains of SF-36. Trials with the new DMARDs, as well as MTX, indicate that long term benefits in radiographic damage and physical function can be inferred from treatment data over 12 months. "Successful" patients who continue to do well will derive benefit from treatment for as long as 3 to 5 years. Recent RCTs indicate that combination therapy, initiated together, offers more improvement in radiographic progression and physical function than monotherapy, although the trial data cannot yet tell us which DMARD may be most beneficial in a given patient. Once treatment with any one agent--biologic or synthetic--is initiated, the addition of a second agent should occur rapidly, if for example active disease persists 8 or 12 weeks later, without waiting for documented treatment failure. If this treatment paradigm is followed, along with regular assessments of radiographic damage and physical function, then patients may more likely derive long term clinical benefit than with traditional approaches.