Chikungunya virus (CHIKV) infection generally causes a debilitating arthritis in infected patients. Infection with CHIKV is generally not life-threatening and is associated with a mortality rate <0.1%. However, close to 100% of those infected will develop symptoms of disease, primarily involving swelling and pain of the joints, which can last for months or even years. A model that mimics these symptoms is needed for thedevelopment of therapies to ameliorate disease and control viral infection. In this chapter, we describe the establishment of a model of CHIKV infection in mice that is nonlethal and utilizes footpad swelling and virus titer of various tissues as key disease parameters. This model was developed primarily for use in evaluating the in vivo efficacy of candidate antiviral agents, although important questions regarding basic biology and pathogenesis of the disease may also be elucidated using this system.