The family Togaviridae consists of two genera, Alphavirus and Rubivirus (Fields et al., 2013). The organization of their respective genomes is similar, but phylogenetic analysis shows that alphaviruses and rubiviruses are quite divergent (Koonin and Dolja, 1993). This book focuses on the genus Alphavirus, which consists of small (45 to 75 nm in diameter), enveloped viruses, typically transmitted by arthropod vectors, including mosquitoes, mites and ticks (Powers et al., 2001). Approximately 30 species of Alphavirus have been identified and differentiated into seven groups based on antigen similarity determined by serum neutralization. These antigenic groups are the Barmah Forest complex, the Ndumu complex, the Middelburg complex, Semliki Forest complex, Western equine encephalitis complex, Eastern equine encephalitis complex, and Venezuelan equine encephalitis complex (Powers et al., 2001). All seven serotypes share similarity in both genome organization (having two open reading frame encoding both the structural and nonstructural proteins) and viral replication cycle (which includes virus binding, entry, replication and release). This chapter will focus on the alphaviral genome and the events of alphaviral replication.