Treatments for rheumatoid arthritis (RA) have involved a variety of single agent and combination therapies with one paramount goal, to slow disease progression and bone destruction. However, data indicate that not all drug combinations are equally efficacious in all patients with RA, and toxicity levels can be difficult to manage. In addition to these concerns, studies are difficult to compare because of methodologic differences and differing drug doses and schedules, for example. To more accurately discern how to best manage early RA, and because treating RA within 3 months of diagnosis appears crucial for improved outcomes, this review summarizes studies that compared combination to monotherapies in early RA, while attempting to consider factors that could complicate the results. These reports utilized disease modifying antirheumatic drugs (DMARD) with known efficacy among patients with RA, but more importantly a number also used varying levels of glucocorticoids as well. Collectively, these data are beginning to shed light on how to best treat early RA, suggesting that DMARD work best when given very early.