Post-streptococcal reactive arthritis is a frequently observed entity that has an uncertain relationship with acute rheumatic fever. Although different criteria have been suggested for delineating these two conditions, none have been validated. In the absence of a clear definition, it has been impossible for investigators to carry out meaningful studies. Some children who were initially labeled as having post-streptococcal reactive arthritis later suffered from carditis and definite rheumatic fever with subsequent streptococcal infections. Some physicians now recommend that all children with post-streptococcal reactive arthritis receive penicillin prophylaxis. However, the proper duration of treatment and appropriate guidelines for patient selection have not been determined. It will be impossible to answer these questions until collaborative efforts are made to accurately define this illness and then begin a careful analysis of its etiopathogenesis and natural history. In the interim, each physician must evaluate the potential risks and benefits of penicillin prophylaxis in view of the risk of rheumatic fever in the community.