It is now accepted that rheumatoid arthritis is not a benign disease, and has considerable morbidity and increased mortality rates. Monotherapy with disease modifying anti-rheumatic drugs (DMARDs) is often ineffective, and rarely leads to sustained clinical remission. Many clinical trials suggest the effectiveness of using combination therapies, and also the benefit of aggressive management early in the course of the disease. However, recent publications studying a variety of combination therapies in rheumatoid arthritis have shown diverse results. Drug combinations at an early stage of rheumatoid arthritis which slow radiographic progression appear to be the most convincing. These data suggest that practitioners should begin with intensive therapy in early disease, and not reserve combination therapy for those who fail monotherapy. The therapeutic strategy should be positioned according to the severity of the disease: in RA with markers indicating severity, combination should be initiated at the start of therapy while it should be instituted in a rapid step-up fashion in mild RA if insufficient efficacy is seen for monotherapy. In general, combinations appear safe and well-tolerated, but continued caution with appropriate monitoring of long-term results and possible toxicities is required.