Early diagnosis and therapeutic intervention are needed to prevent the morbidity related to erosive arthropathies such as rheumatoid arthritis (RA), yet it is difficult to distinguish various forms of synovitis early in the disease course. The availability of synovial tissue biopsy techniques has facilitated the analysis of synovial tissue from patients with early disease. Comparison of the histopathologic features of synovial tissue in early RA, established RA, and in non-RA synovitis has shown subtle, but potentially important differences in histologic features, cytokine and protease expression patterns, and apoptosis. Ultimately, it remains to be shown definitively that analysis of the histopathological features of synovial tissue early in disease is of independent value in identifying patients destined to have persistent synovitis or erosive disease, and in turn, in allocating patients to specific therapeutic strategies.