The emergence of zoonotic viruses maintained by wildlife reservoir hosts is poorly understood. Recent discoveries of Hendra (HENV) and Nipah (NIPV) viruses in Australasia and the emergence of epidemic West Nile virus (WNV) in the United States have added urgency to the study of cross-species transmission. The processes by which zoonotic viruses are transmitted and infect other species are examined as four transitions. Two of these, inter-species contact and cross-species virus transmission (spillover), are essential and sufficient to cause epidemic emergence. Sustained transmission and virus adaptation within the spillover host are transitions not required for virus emergence, but determine the magnitude and scope of subsequent disease outbreaks. Ecologic, anthropogenic, and evolutionary factors modify the probability that viruses complete or move through transitions. As surveillance for wildlife diseases is rare and often outbreak-driven, targeted studies are required to elucidate the means by which important zoonotic viruses are maintained and spillover occurs.