The use of molecular techniques in epidemiology gives a better understanding of viral transmission and diversity, and helps to define and characterizc outbreaks. By elucidating transmission patterns and defining outbreak parameters, appropriate preventive measures can be implemented in a timely fashion. Previously, the understanding of viral classification and phylogeny was difficult due to the challenges inherent in studying viruses. Automated cycle sequencing that uses fluorescently labeled nucleotides has revolutionized epidemiological studies of viruses at the molecular level. Sequencing of viral genes enables the identification and characterization of viruses, and sequence data are essential when investigating the etiology, dissemination, and transmission of viral infections as well as for disease surveillance and prevention. The present chapter focuses on the use of sequence analyses in epidemiological investigations.