Rheumatoid arthritis is a systemic, inflammatory, autoimmune disorder. Enhanced understanding of molecular pathogenesis has enabled development of innovative biological agents that target specific parts of the immune system. These treatments have changed the course and face of rheumatoid arthritis and outcomes for patients and society. New knowledge has emerged of how environmental factors interact with susceptibility genes and the immune system in the pathogenesis of a major subset of rheumatoid arthritis. Research undertaken on the longitudinal disease process and molecular pathology of joint inflammation has led to new therapeutic strategies that promote early use of disease-modifying drugs with tight disease control and distinct and quantifiable treatment goals. Today, such approaches can halt most cases of joint destruction but not all instances of joint inflammation and comorbidity. Understanding the cause and pathogenesis of different rheumatoid arthritis subsets will lead not only to individualised treatments during early phases of the illness but also, possibly, to disease prevention.