Alphaviruses are emerging human pathogens that are transmitted by arthropod vectors. Their ability to infect a wide range of vertebrate hosts including humans, equines, birds and rodents has brought about a series of epidemic and epizootic outbreaks worldwide. Their potential to cause a pandemic has spurred the interest of researchers globally, leading to the rapid advancement on the characterization of genetic determinants of alphaviruses. In this review, the focal point is placed on the genetics of alphaviruses, whereby the genetic composition, clinical features, evolution and adaptation of alphaviruses, modulation of IFN response by alphavirus proteins and therapeutic aspects of alphaviruses will be discussed.