Recent emphasis on early diagnosis and treatment of rheumatoid arthritis (RA) to improve long-term disease outcome has raised important questions about optimal therapy for early RA. With an expanding armamentarium of disease-modifying antirheumatic drugs including biological agents, there are now several therapeutic choices available to clinicians. However, at early stages of arthritis, difficulty in accurately predicting individual prognosis and response to therapy continues to pose a significant challenge. Future research in biomarkers of progressive, erosive disease and controlled trials to establish the most effective therapies in early RA will greatly enhance our ability to minimize the impact of this potentially disabling disease.