In the multifactorial etiology of rheumatic diseases, infectious agents are regarded as the major environmental factors that may cause inflammatory arthritides in genetically susceptible hosts. Two not mutually exclusive pathogenetic pathways are hypothesized to explain the initiation and perpetuation of chronic arthritides by infectious agents: persistent infection and induction of immunopathology. In this review we focus on the role of infections in the etiopathogenesis of rheumatoid arthritis. Retroviruses and enteropathogenic bacteria continue to be the most intensively discussed candidates as possible etiologic factors of rheumatoid arthritis. Although there is ample indirect evidence for the involvement of infections in the pathogenesis of autoimmune disease, direct proof is still missing. There may be no single infectious trigger for rheumatoid arthritis, but multiple infectious agents that share antigenic motifs. The "reverse immunology" approach addresses this issue and is discussed in our outlook on future research directions.