Tumor necrosis factor (TNF) is a cytokine associated with the pathogenesis of rheumatoid arthritis. Tumor necrosis factor inhibitors have become important biological treatments that favorably alter the natural history of rheumatoid disease. Side effects include an increased risk of malignancy and infection, particularly tuberculosis. We present 2 patients with rheumatoid arthritis on TNF inhibitors in whom flares of wrist tenosynovitis, initially diagnosed as rheumatoid disease exacerbations, were caused by infections with uncommon opportunistic pathogens. Diagnostic and treatment recommendations for this subset of rheumatoid patients are discussed. © 2010 American Society for Surgery of the Hand.