Identifying viral infections related to rheumatic syndromes and understanding the pathophysiologic mechanisms by which they cause disease are crucial steps to furthering our understanding of the pathogenesis of rheumatic disease. Many common viral infections can induce autoantibody formation. Parvovirus B19 (B19) can cause acute arthritis, and occasionally chronic arthropathy, in infected adults. Persistent B19 infection can be found in synovium of some patients. Antibodies reactive with B19 epitopes can cross react with some autoantigens. Studies of rheumatic syndromes associated with other viral infections, including alphaviruses, rubella, hepatitis C, and retroviruses, suggest differing mechanisms of host interaction with the infectious agents to cause disease.