Virus-induced inflammatory diseases, including arthritis, pneumonia and encephalitis, are a significant cause of human morbidity and mortality. There is a clear need to improve our understanding of the pathogenesis of this diverse array of conditions. In recent years my laboratory has unravelled the mechanisms of how alphaviruses cause musculoskeletal disease (arthritis, arthralgia, myositis). Alphaviruses are the most common cause of musculoskeletal disease worldwide. Alphaviruses have caused explosive epidemics involving thousands to millions of patients, with several recently emerging in new geographic locations. My laboratory has carried out extensive work in understanding the pathogenesis of alphaviral disease and identifying new mechanisms, which has led to the identification of new candidate therapies for viral arthritides. These mechanisms and recent studies in humans will be discussed.