The increased activity of Dengue virus in the tropical regions of the world and the recent movement of West Nile virus from the eastern to the western hemisphere emphasize the fact that vector-borne flaviviruses are medically important emerging infectious diseases. These facts warrant continued efforts to decode all facets of flavivirus immunology. This chapter reviews current understanding of the antigenic fine structure of flaviviral structural and nonstructural (NS) proteins and their involvement in B- an T-cell host responses. The virion structural glycoprotein E elicits both virus-neutralizing antibodies and antiviral Th-cell responses. Consistent with the current hypothesis of the MHC class I pathway of protein processing, immunodominant flaviviral Tc-cell epitopes mainly reside on the NS proteins. To prepare effective and inexpensive subunit vaccines, we will need to continue to better understand these structure-function relationships of flavivirus proteins.