This chapter discusses the evolution of severe acute respiratory syndrome (SARS) coronavirus and the relevance of modern molecular epidemiology. The first case was reported in China in November 2002 and led to a disastrous worldwide pandemic. An international SARS network was established by WHO to rapidly identify the causative agent. In March 2003, the SARS coronavirus was identified. The majority of the early cases were limited to the Guangdong province of China, which have a unique dietary tradition favoring freshly slaughtered game meat; therefore, studies were conducted in those markets for evidence of SARS-CoV. Antibodies against SARS-CoV were detected in masked palm civets. By using serological and PCR surveillance, it was discovered that SARS-like CoV or SL-CoVs were present in different horseshoe bats in the genus Rhinolophus and that they are the likely natural reservoir hosts of bat SL-CoVs. There are more than 60 different horseshoe species around the world, and one or more of them may serve as the natural reservoir of SARS-CoV and/or its progenitor virus(es). It is therefore likely that another outbreak could occur on a similar scale as that of the SARS-CoV outbreaks but our response to a future outbreak caused by any bat-borne coronavirus will be much more effective. SARS is an example demonstrating the evolution of an animal virus into a human pathogen responsible for one of the most severe global pandemic. It is paramount that from now we include active surveillance of wild animals as part of an integrated infectious disease prevention and control strategy.