The association between microbes and joints has existed since antiquity, and remains complex. Diagnosis is often times difficult to determine despite highly suspicious clinical characteristics for the presence of an underlying infection. Over the several past decades, considerable advances have occurred in diagnostic methodologies and therapy. However, the morbidity and mortality of septic arthritis remains high. Great advances have occurred in the diagnosis, pathogenesis, and therapeutic management of reactive arthritis, and there is evidence that when the responsible microorganism is Chlamydia trachomathis, complete remission and cure is possible. Emergent infections, especially viral, has been recognized, i.e. HIV, hepatitis C, and most recently Chikengunya virus, and in the case of HIV associated articular manifestations, the introduction of HAART has resulted in a decrease in the incidence and development of newer complications such as the immune reconstitution syndrome. The infectious etiology of rheumatoid arthritis is being strongly considered once again, and the exciting association with periodontal disease is at the forefront of intense research. The gut microbiota is also being investigated and new and most interesting data is being gathered of the potential role of commensal gut organisms and the pathogenesis of rheumatoid arthritis.