Chikungunya virus (CHIKV) is an arbovirus responsible for acute febrile arthralgia. It re-emerged abruptly in 2005 and caused a massive outbreak in the Indian Ocean region, and then extended to Asia. Here we review the pathophysiology of CHIKV infection, based on human and mouse studies, and also present prospects for prevention and therapy of this infection. Our results are discussed in the light of the current knowledge regarding other arthritogenic Alphaviruses.