Persistent inflammatory monoarthritis is inflammation of one joint, with symptoms lasting beyond 3 months. Approximately 50 % of cases are self-limiting; others will transform into oligo- or polyarticular disease, but a significant minority remain as a persistent inflammatory monoarthritis, which are often resistant to standard therapies used for oligo- or polyarticular disease and constitute a difficult therapeutic problem. However, there are no clear guidelines for treatment of this category of patients or an evidence-based consensus view on best treatment. A literature search was done through PubMed using 'monoarthritis', 'chronic synovitis' and 'persistent inflammatory monoarthritis' as search terms. Reports were located using references to related articles; reports in humans and animals, published in English, were included. Persistent inflammatory monoarthritis has a variable disease course, generally with a better prognosis than polyarthritis. There is no clear evidence for the use of traditional DMARDS in monoarthritis, and treatment algorithms are extrapolated from oligo- or polyarticular disease. Intra-articular anti-tumour necrosis factor (TNF) has been used with similar efficacy to intra-articular corticosteroids, and as yet, there are no reported cases of systemic anti-TNF use in monoarthritis. Synovectomy may be of use, with lower risk of recurrent disease, in open synovectomy. There is paucity of evidence for best practice in the management of chronic monoarthritis. Questions remain concerning the indications for invasive procedures and the balance between toxicity of systemic therapies versus the intended benefits to prevent disability. There is a pressing need for further studies and randomised controlled trials to be performed in this subset of patients.