Reactive arthritis (ReA), an inflammatory arthritic condition that is commonly associated with Chlamydia infections, represents a significant health burden, yet is poorly understood. The enigma of this disease is reflected in its problematic name and in its ill-defined pathogenesis. The existence of persistent pathogens in the arthritic joint is acknowledged, but their relevance remains elusive. Progress is being made in understanding the underlying mechanisms of ReA, whereby an imbalance between type 1 and type 2 immune responses seems to be critical in determining susceptibility to disease. Such an imbalance occurs prior to the initiation of an adaptive immune response, suggesting that innate cellular and molecular mechanisms in ReA should be prioritized as fruitful areas for investigation.